Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6PKBN)

• DTT Name: Proto-oncogene c-Src (SRC)
• Synonyms: pp60c-src; Tyrosine kinase (pp60(src)); Src tyrosine kinase; SRC1; Proto-oncogene tyrosine-protein kinase Src; Pp60(src); P60-Src; C-src TK; C-Src
• Gene Name: SRC
• DTT Type: Successful target; [1]
• Related Disease:
  Breast cancer [ICD-11: 2C60-2C6Y]
  Ischemia [ICD-11: 8B10-8B11]
  Myeloproliferative neoplasm [ICD-11: 2A20]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• BioChemical Class: Kinase
• UniProt ID: SRC_HUMAN
• TTD ID: T85943
• EC Number: EC 2.7.10.2
• Sequence:
  MGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAE
  PKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGD
  WWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRES
  ETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGL
  CHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTL
  KPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKY
  LRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYT
  ARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVER
  GYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
• Function: Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Involved in anchorage-independent cell growth. Required for podosome formation. Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors.
• KEGG Pathway:
  ErbB signaling pathway (hsa04012)
  Rap1 signaling pathway (hsa04015)
  Chemokine signaling pathway (hsa04062)
  Endocytosis (hsa04144)
  VEGF signaling pathway (hsa04370)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Gap junction (hsa04540)
  Platelet activation (hsa04611)
  GABAergic synapse (hsa04727)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Regulation of actin cytoskeleton (hsa04810)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Prolactin signaling pathway (hsa04917)
  Thyroid hormone signaling pathway (hsa04919)
  Oxytocin signaling pathway (hsa04921)
  Bacterial invasion of epithelial cells (hsa05100)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Shigellosis (hsa05131)
  Tuberculosis (hsa05152)
  Hepatitis B (hsa05161)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  Nuclear signaling by ERBB4 (R-HSA-1251985)
  Downregulation of ERBB4 signaling (R-HSA-1253288)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Spry regulation of FGF signaling (R-HSA-1295596)
  Signaling by SCF-KIT (R-HSA-1433557)
  Regulation of KIT signaling (R-HSA-1433559)
  p38MAPK events (R-HSA-171007)
  Signaling by EGFR (R-HSA-177929)
  GAB1 signalosome (R-HSA-180292)
  Downstream signal transduction (R-HSA-186763)
  Regulation of gap junction activity (R-HSA-191650)
  Signaling by ALK (R-HSA-201556)
  FCGR activation (R-HSA-2029481)
  PECAM1 interactions (R-HSA-210990)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  EPH-Ephrin signaling (R-HSA-2682334)
  Integrin signaling (R-HSA-354192)
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  NCAM signaling for neurite out-growth (R-HSA-375165)
  CD28 co-stimulation (R-HSA-389356)
  CTLA4 inhibitory signaling (R-HSA-389513)
  Signal regulatory protein family interactions (R-HSA-391160)
  EPHB-mediated forward signaling (R-HSA-3928662)
  EPHA-mediated growth cone collapse (R-HSA-3928663)
  Ephrin signaling (R-HSA-3928664)
  EPH-ephrin mediated repulsion of cells (R-HSA-3928665)
  G alpha (s) signalling events (R-HSA-418555)
  ADP signalling through P2Y purinoceptor 1 (R-HSA-418592)
  G alpha (i) signalling events (R-HSA-418594)
  DCC mediated attractive signaling (R-HSA-418885)
  Netrin mediated repulsion signals (R-HSA-418886)
  Regulation of commissural axon pathfinding by SLIT and ROBO (R-HSA-428542)
  GP1b-IX-V activation signalling (R-HSA-430116)
  Recycling pathway of L1 (R-HSA-437239)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  VEGFR2 mediated cell proliferation (R-HSA-5218921)
  CLEC7A (Dectin-1) signaling (R-HSA-5607764)
  RHO GTPases Activate Formins (R-HSA-5663220)
  RAF activation (R-HSA-5673000)
  MAP2K and MAPK activation (R-HSA-5674135)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Cyclin D associated events in G1 (R-HSA-69231)
  RET signaling (R-HSA-8853659)
  MET activates PTK2 signaling (R-HSA-8874081)
  InlA-mediated entry of Listeria monocytogenes into host cells (R-HSA-8876493)
  Regulation of RUNX1 Expression and Activity (R-HSA-8934593)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  Regulation of RUNX3 expression and activity (R-HSA-8941858)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  RHOU GTPase cycle (R-HSA-9013420)
  Activated NTRK2 signals through FYN (R-HSA-9032500)
  Activated NTRK3 signals through PI3K (R-HSA-9603381)
  Long-term potentiation (R-HSA-9620244)
  GPER1 signaling (R-HSA-9634597)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  FCGR3A-mediated IL10 synthesis (R-HSA-9664323)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  Signaling by ERBB2 (R-HSA-1227986)
• BioCyc Pathway: MetaCyc:HS02256-MON

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[2]
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[2], [3], [4]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[1]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[5]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[6]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[6]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[7]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[8]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[9]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[11]
KX2-361	DML4H05	Brain cancer	2A00	Phase 1	[12]
SUN-K0706	DMIF8RY	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[6], [13]
TPX-0022	DMC2IJN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]

9 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aromatic bicyclic compound 1	DMVLQ2P	N. A.	N. A.	Patented	[15]
Aromatic bicyclic compound 2	DMKFV67	N. A.	N. A.	Patented	[15]
Aromatic bicyclic compound 3	DMRXN94	N. A.	N. A.	Patented	[15]
Aromatic bicyclic compound 4	DM3E75P	N. A.	N. A.	Patented	[15]
Aromatic bicyclic compound 5	DMALF06	N. A.	N. A.	Patented	[15]
Aromatic bicyclic compound 6	DM8L3KM	N. A.	N. A.	Patented	[15]
Deuterated 3-cyanoquinoline derivative 1	DM3Q9OX	N. A.	N. A.	Patented	[16]
PMID28460551-Compound-6	DMT7U1O	N. A.	N. A.	Patented	[17]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[18]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AP22408	DM5B72D	Osteoporosis	FB83.0	Terminated	[19]
PD166285	DMAOHXY	N. A.	N. A.	Terminated	[20]

98 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(4-CARCOXY-5-ISOPROPYLTHIAZOLYL)BENZOPIPERIDINE	DM2XFGJ	Discovery agent	N.A.	Investigative	[21]
3-(3-aminobenzo[e][1,2,4]triazin-7-yl)phenol	DMLYVPH	Discovery agent	N.A.	Investigative	[22]
4-Chloro-5,7-diphenyl-7H-pyrrolo[2,3-d]pyrimidine	DMI580M	Discovery agent	N.A.	Investigative	[23]
5,7-Diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol	DMKXIWQ	Discovery agent	N.A.	Investigative	[23]
7-(naphthalen-2-yl)benzo[e][1,2,4]triazin-3-amine	DMU74R8	Discovery agent	N.A.	Investigative	[22]
A-420983	DM7HSCI	Discovery agent	N.A.	Investigative	[24]
A-770041	DMP78JY	Discovery agent	N.A.	Investigative	[25]
Ac-Cys-Ile-cyclo[Phe-Lys]-Tyr-Tyr	DMH0SQC	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Phe(4-NO2)-Lys-Phe(4-NO2)-Tyr	DMG19LW	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Phe(4-NO2)-Lys-Tyr-Phe(4-NO2)	DMORPDV	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Phe(4-NO2)-Lys-Tyr-Tyr	DMK7YIG	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-Cl)-Tyr	DMUWI2F	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-CN)-Tyr	DMNW7GR	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-I)-Tyr	DMO4MYI	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-N3)-Tyr	DME4FZD	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-NO2)-Phe(4-NO2)	DM856JM	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Phe(4-NO2)-Tyr-Phe	DMU2PT1	Discovery agent	N.A.	Investigative	[26]
Ac-Cys-Ile-Tyr-Lys-Tyr-Phe(4-NO2)	DM4MP69	Discovery agent	N.A.	Investigative	[26]
AP-24163	DMVT6Y3	Discovery agent	N.A.	Investigative	[27]
AP-24226	DMGTEXD	Discovery agent	N.A.	Investigative	[27]
BAS-00387275	DMZPKGS	Discovery agent	N.A.	Investigative	[28]
BAS-00387328	DM4OSFD	Discovery agent	N.A.	Investigative	[28]
BAS-00387347	DMUF28Q	Discovery agent	N.A.	Investigative	[28]
BAS-00672722	DM6R4X8	Discovery agent	N.A.	Investigative	[28]
BAS-01047341	DMNB7CW	Discovery agent	N.A.	Investigative	[28]
BAS-01047655	DMC0FLB	Discovery agent	N.A.	Investigative	[28]
BAS-01373578	DMZBIC3	Discovery agent	N.A.	Investigative	[28]
BAS-0338868	DMZGLHJ	Discovery agent	N.A.	Investigative	[29]
BAS-0338872	DMZK0SC	Discovery agent	N.A.	Investigative	[29]
BAS-09534324	DMFMBZ9	Discovery agent	N.A.	Investigative	[28]
BAS-450225	DMTH1JQ	Discovery agent	N.A.	Investigative	[28]
BAS-4844343	DMFNAKU	Discovery agent	N.A.	Investigative	[28]
BMS-279700	DMOLCFQ	Discovery agent	N.A.	Investigative	[30]
CGP 77675	DMXH2R3	Discovery agent	N.A.	Investigative	[31]
CGP-191	DMCE6WJ	Discovery agent	N.A.	Investigative	[23]
CGP-62464	DMZ34P1	Discovery agent	N.A.	Investigative	[23]
Cyclo[Ac-Cys-Ile-Phe]-Lys-Tyr-Tyr	DM67CAY	Discovery agent	N.A.	Investigative	[26]
Cyclo[Ac-Cys-Ile-Tyr-Lys-Tyr-Phe]	DMB2DV1	Discovery agent	N.A.	Investigative	[26]
Cyclo[Ac-Cys-Ile-Tyr-Lys-Tyr-Tyr]	DMO5V9M	Discovery agent	N.A.	Investigative	[26]
Cysteine Sulfenic Acid	DM4GZUJ	N. A.	N. A.	Investigative	[32]
DPI59	DMTHZ3B	Discovery agent	N.A.	Investigative	[21]
Glu-Pro-Gln-F2Pmp-Glu-Glu-Ile-Pro-Ile-Tyr-Leu	DM6EA9B	Discovery agent	N.A.	Investigative	[33]
Glu-Pro-Gln-pTyr-Glu-Glu-Ile-Pro-Ile-Tyr-Leu	DMYZO37	Discovery agent	N.A.	Investigative	[33]
HKI-9924129	DM5LR2B	Gram-positive bacterial infection	1B74-1G40	Investigative	[34]
ISO24	DMU64W8	Discovery agent	N.A.	Investigative	[21]
JNJ-10198409	DM9GDP5	Discovery agent	N.A.	Investigative	[35]
K00244	DM2BKU8	Discovery agent	N.A.	Investigative	[36]
N-(4-(phenylamino)quinazolin-6-yl)acrylamide	DMI74KM	N. A.	N. A.	Investigative	[21]
N-Phenyl-5-phenylimidazo[1,5-a]pyrazin-8-amine	DMGVJBD	Discovery agent	N.A.	Investigative	[30]
N6-Benzyl Adenosine-5'-Diphosphate	DM71MO2	Discovery agent	N.A.	Investigative	[37]
NG-25	DMC48D9	Discovery agent	N.A.	Investigative	[38]
NM-PP1	DMS8H5Q	Discovery agent	N.A.	Investigative	[11]
Oxalic Acid	DMLN2GQ	Discovery agent	N.A.	Investigative	[37]
PAS219	DML8BT7	Discovery agent	N.A.	Investigative	[21]
PASBN	DM7Y0G6	Discovery agent	N.A.	Investigative	[21]
PD-0166326	DMD2CG9	Discovery agent	N.A.	Investigative	[39]
PD-0173952	DMSCQ9U	Discovery agent	N.A.	Investigative	[34]
PD-0173955	DMOZEW9	Discovery agent	N.A.	Investigative	[34]
PD-0173956	DM8RW92	Discovery agent	N.A.	Investigative	[39]
PD-0173958	DMZQ8YV	Discovery agent	N.A.	Investigative	[34]
PD-0179483	DMKO8LE	Discovery agent	N.A.	Investigative	[34]
PD-174265	DMBHIAK	Discovery agent	N.A.	Investigative	[40]
PD173074	DMP0N4U	Nasopharyngeal carcinoma	2B6B	Investigative	[20]
Phenylphosphate	DMQ6P13	Discovery agent	N.A.	Investigative	[32]
Phosphonotyrosine	DM09MY1	Discovery agent	N.A.	Investigative	[37]
PMID15546730C2	DMOPUIH	Discovery agent	N.A.	Investigative	[41]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[42]
PP121	DMU8KTO	Discovery agent	N.A.	Investigative	[43]
RU78191	DMOQE91	Discovery agent	N.A.	Investigative	[21]
RU78262	DMR8I03	Discovery agent	N.A.	Investigative	[21]
RU78299	DMXAK92	Discovery agent	N.A.	Investigative	[21]
RU78300	DM27BKD	Discovery agent	N.A.	Investigative	[21]
RU78783	DMU5H4K	Discovery agent	N.A.	Investigative	[37]
RU79072	DM9GQP0	Discovery agent	N.A.	Investigative	[21]
RU79073	DMWKTYC	Discovery agent	N.A.	Investigative	[21]
RU79256	DM06BGV	Discovery agent	N.A.	Investigative	[21]
RU81843	DMY3X6I	Discovery agent	N.A.	Investigative	[37]
RU82129	DMX7ZI0	Discovery agent	N.A.	Investigative	[37]
RU82197	DMJG4RC	Discovery agent	N.A.	Investigative	[32]
RU82209	DMR3A2O	Discovery agent	N.A.	Investigative	[37]
RU83876	DMNGKYF	Discovery agent	N.A.	Investigative	[37]
RU84687	DMWK3LU	Discovery agent	N.A.	Investigative	[21]
RU85053	DMOA8FK	Discovery agent	N.A.	Investigative	[37]
RU85493	DM97ZHX	Discovery agent	N.A.	Investigative	[37]
RU90395	DMHFKUC	Discovery agent	N.A.	Investigative	[37]
SBB007833	DMU8KGB	Discovery agent	N.A.	Investigative	[44]
SKS-927	DMGQ9Z5	Discovery agent	N.A.	Investigative	[45]
SU 6656	DMF1P6W	Discovery agent	N.A.	Investigative	[11]
TG-100435	DMIR3X2	Discovery agent	N.A.	Investigative	[46]
WH-4-023	DMJS8VQ	Discovery agent	N.A.	Investigative	[47]
Y-c[D-Pen-(2')Nal-GSFC]KR-NH2	DMAC65P	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(2R,3R)-2-Me-(2')Nal-GSFC]KR-NH2	DMEL4UN	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(2R,3S)-2-Me-(2')Nal-GSFC]KR-NH2	DM7P0H6	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(2S,3R)-2-Me-(2')Nal-GSFC]KR-NH2	DMBNM85	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(2S,3S)-2-Me-(2')Nal-GSFC]KR-NH2	DME1BGO	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(3,5-diI)Tyr-GSFC]KR-NH2	DMF7S54	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-(3-I)Tyr-GSFC]KR-NH2	DMW1PSO	Discovery agent	N.A.	Investigative	[48]
Y-c[D-Pen-D-(2')Nal-GSFC]KR-NH2	DM2ILAH	Discovery agent	N.A.	Investigative	[48]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Glioma	2C82	Brainstem tissue	6.45E-01	-0.08	-0.58
Glioma	2C82	White matter	2.08E-03	-0.52	-1.62
Multiple myeloma	2C82	Bone marrow	7.46E-03	-0.2	-1.24
Breast cancer	2C82	Breast tissue	1.51E-04	-0.07	-0.28
Osteoporosis	FA20	Bone marrow	4.20E-02	0.26	6.22
Neuroectodermal tumour	2C82	Nervous tissue	1.26E-29	-0.2	-0.64
Prostate cancer	2C82	Prostate	8.62E-01	-0.17	-0.45
Sarcoma	2C82	Muscle tissue	2.35E-48	-0.19	-0.78

References

• [1] In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
• [2] A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
• [3] In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc. J Clin Pharmacol. 2008 Oct;48(10):1179-88.
• [4] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [5] Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [10] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [11] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [12] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2206).
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [15] A STAT inhibitor patent review: progress since 2011.Expert Opin Ther Pat. 2015;25(12):1397-421.
• [16] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [17] Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jul;27(7):753-761.
• [18] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [19] Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9373-8.
• [20] Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy. Invest New Drugs. 1999;17(2):121-35.
• [21] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [22] Discovery and preliminary structure-activity relationship studies of novel benzotriazine based compounds as Src inhibitors. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5546-50.
• [23] Substituted 5,7-diphenyl-pyrrolo[2,3d]pyrimidines: potent inhibitors of the tyrosine kinase c-Src. Bioorg Med Chem Lett. 2000 May 1;10(9):945-9.
• [24] A-420983: a potent, orally active inhibitor of lck with efficacy in a model of transplant rejection. Bioorg Med Chem Lett. 2004 May 17;14(10):2613-6.
• [25] Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection. Bioorg Med Chem Lett. 2006 Jan 1;16(1):118-22.
• [26] Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibi... J Med Chem. 2006 Jun 1;49(11):3395-401.
• [27] 9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation. J Med Chem. 2009 Aug 13;52(15):4743-56.
• [28] A combination of docking/dynamics simulations and pharmacophoric modeling to discover new dual c-Src/Abl kinase inhibitors. J Med Chem. 2006 Jun 1;49(11):3278-86.
• [29] Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1207-11.
• [30] Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for treatment of acute ischemic stroke. Bioorg Med Chem. 2007 Jan 15;15(2):868-85.
• [31] A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999 May;24(5):437-49.
• [32] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [33] The Role of 4-phosphonodifluoromethyl- and 4-phosphono-phenylalanine in the selectivity and cellular uptake of SH2 domain ligands, Bioorg. Med. Chem. Lett. 7(14):1909-1914 (1997).
• [34] Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98.
• [35] (6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad ant... J Med Chem. 2005 Dec 29;48(26):8163-73.
• [36] The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92.
• [37] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [38] Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 8;58(1):183-96.
• [39] Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6.
• [40] Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc. J Med Chem. 2009 Jul 9;52(13):3915-26.
• [41] Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6061-6.
• [42] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [43] Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol. 2008 Nov;4(11):691-9.
• [44] Synthesis and pharmacological evaluation of novel beta-nitrostyrene derivatives as tyrosine kinase inhibitors with potent antiplatelet activity. Biochem Pharmacol. 2007 Aug 15;74(4):601-11.
• [45] Inhibition of Src kinase activity by 7-ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of SKS-927. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1358-61.
• [46] Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinas... Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8.
• [47] Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity. J Med Chem. 2006 Aug 10;49(16):4981-91.
• [48] Discovery of a novel series of potent and selective substrate-based inhibitors of p60c-src protein tyrosine kinase: conformational and topographica... J Med Chem. 1998 Jun 18;41(13):2252-60.