Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM9J50F)

• Drug Name: KT-5720 Drug Info
• Synonyms: KT 5720; KT5720; 108068-98-0; GTPL337; ZINC3873013; KT 5720, > hexyl (15R,16R,18S)-16-hydroxy-15-methyl-3-oxo-28-oxa-4,14,19-triazaoctacyclo[12.11.2.1^{15,18}.0^{2,6}.0^{7,27}.0^{8,13}.0^{19,26}.0^{20,25}]octacosa-1(26),2(6),7(27),8,10,12,20,22,24-nonaene-16-carboxylate; (9S,10S,12R)-2,3,9,10,11,12-Hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3 inverted exclamation marka,2 inverted exclamation marka,1 inverted exclamation marka-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-c

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 454202
  ChEBI ID: CHEBI:85085
  CAS Number: CAS 108068-98-0
  TTD Drug ID: DM9J50F

Molecule-Related Drug Atlas

Drug(s) Targeting Protein kinase C alpha (PRKCA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium phenylbutyrate	DMXLBCQ	Spinal muscular atrophy	8B61	Approved	[4]
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[5]
PMID28460551-Compound-3	DMA1FRM	N. A.	N. A.	Patented	[6]
ISIS 3521	DMZFS69	N. A.	N. A.	Discontinued in Phase 2	[7]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[8]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[9]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[10]
Acteoside	DM0YHKB	Nephritis	GB40	Terminated	[11]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[12]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[13]

Drug(s) Targeting Stress-activated protein kinase JNK1 (JNK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NKP-1339	DM5AWK1	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[15]
7-azaindole derivative 1	DMQL5B7	N. A.	N. A.	Patented	[15]
7-azaindole derivative 5	DMV3H98	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-P6	DMNDVC9	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-J3	DM17P3F	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-P1	DMD8AX6	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-O3	DMVOWS5	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[15]

Drug(s) Targeting Rho-associated protein kinase 1 (ROCK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Netarsudil	DM0LPI9	Open-angle glaucoma	9C61	Approved	[16]
SAR-407899	DMF95KD	Diabetic nephropathy	GB61.Z	Phase 2	[17]
H-1152	DM8XH3S	Pulmonary arterial hypertension	BB01.0	Phase 2	[18]
INS-117548	DMA46DO	Glaucoma/ocular hypertension	9C61	Phase 1	[19]
GSK269962A	DM5I2HL	Inflammation	1A00-CA43.1	Clinical trial	[20]
PMID28048944-Compound-19	DMPT3V9	N. A.	N. A.	Patented	[21]
PMID28048944-Compound-3	DM1BN74	N. A.	N. A.	Patented	[21]
PMID28048944-Compound-7	DMXZ368	N. A.	N. A.	Patented	[21]
PMID28048944-Compound-4	DMJAUWG	N. A.	N. A.	Patented	[21]
PMID28048944-Compound-5	DMAB987	N. A.	N. A.	Patented	[21]

Drug(s) Targeting Stress-activated protein kinase 2b (p38 beta)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[22]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[22]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[2]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[13]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[2]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[2]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[2]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[23]

Drug(s) Targeting Extracellular signal-regulated kinase 2 (ERK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BVD-523	DMNB4XK	Melanoma	2C30	Phase 2	[24]
HH2710	DM0C5MV	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[25]
ASTX029	DMVZXIA	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[26]
VAN-10-4-eluting stent	DM3ZW6A	Artery stenosis	BD52	Phase 1	[27]
GDC-0994	DMFC2OY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[28]
JSI-1187	DMVJWBS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[29]
LY3214996	DMFDAY7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[30]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[31]
COR-D	DMLXMCB	T-cell leukaemia	2A90	Preclinical	[32]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[33]

Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[34]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[34]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[35]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[22]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[34]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[15]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[15]

Drug(s) Targeting MAP kinase p38 (MAPK12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SM-101	DMFX9O6	Idiopathic thrombocytopenic purpura	3B64.10	Approved (orphan drug)	[36]
VX-745	DMJAEG6	Alzheimer disease	8A20	Phase 2	[37]
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[38]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[39]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[40]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[2]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[13]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[41]

Drug(s) Targeting Ribosomal protein S6 kinase beta-1 (S6K1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
M2698	DM3PVBJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[30]
NNI-362	DMPCV65	Alzheimer disease	8A20	Phase 1	[42]
PF-4708671	DMO0892	Ulcerative colitis	DD71	Clinical trial	[43]
PMID27410995-Compound-Figure3c	DMDQMZT	N. A.	N. A.	Patented	[44]
Pyrimido[4,5-d] pyrimidines and pyrido[4,3-d] pyrimidine derivative 1	DM6O2Q9	N. A.	N. A.	Patented	[44]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[45]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[13]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[2]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[2]

Drug(s) Affected By ATP-dependent translocase ABCB1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[46]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[47]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[48]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[49]
Cepharanthine	DM9Y5JB	N. A.	N. A.	Approved	[50]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[51]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[52]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[53]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[54]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[52]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_HUMAN	Inhibitor	[2]
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[2]
Protein kinase C alpha (PRKCA)	TTFJ8Q1	KPCA_HUMAN	Inhibitor	[2]
Rho-associated protein kinase 1 (ROCK1)	TTZN7RP	ROCK1_HUMAN	Inhibitor	[2]
Ribosomal protein S6 kinase beta-1 (S6K1)	TTG0U4H	KS6B1_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[2]
Stress-activated protein kinase JNK1 (JNK1)	TT0K6EO	MK08_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[3]

References

• [1] 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. (Ligand id: 337).
• [2] Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
• [3] Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1. Leuk Res. 2005 Apr;29(4):407-14. doi: 10.1016/j.leukres.2004.09.001.
• [4] Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.Mol Cancer Ther. 2013 Aug;12(8):1393-401.
• [5] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [6] Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jul;27(7):753-761.
• [7] Phase II study of PKC-alpha antisense oligonucleotide aprinocarsen in combination with gemcitabine and carboplatin in patients with advanced non-small cell lung cancer.Lung Cancer.2006 May;52(2):173-80.
• [8] Evaluation of differential hypoxic cytotoxicity and electrochemical studies of nitro 5-deazaflavins, Bioorg. Med. Chem. Lett. 5(18):2155-2160 (1995).
• [9] Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
• [10] Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
• [11] Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity. J Nat Prod. 1998 Nov;61(11):1410-2.
• [12] Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
• [13] Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
• [14] 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: 1496).
• [15] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [16] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [17] The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries. J Hypertens. 2012 May;30(5):980-9.
• [18] Emerging treatments for pulmonary arterial hypertension. Expert Opin Emerg Drugs. 2006 Nov;11(4):609-19.
• [19] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [20] Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.
• [21] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [22] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
• [23] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [24] DOI: 10.1158/1538-7445.AM2015-4693
• [25] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [26] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [27] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [28] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [29] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [30] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [31] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [32] Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway. Cell Physiol Biochem. 2012;30(4):915-26.
• [33] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [34] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [35] Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
• [36] Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
• [37] P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.
• [38] Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
• [39] KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
• [40] Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity. J Med Chem. 2003 Dec 18;46(26):5651-62.
• [41] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [42] Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59.
• [43] Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J. 2010 Oct 15;431(2):245-55.
• [44] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [45] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [46] Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists. Cancer Res. 1994 Feb 1;54(3):730-7.
• [47] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [48] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [49] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [50] Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci. 2005 Jun;96(6):372-6. doi: 10.1111/j.1349-7006.2005.00057.x.
• [51] Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
• [52] Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• [53] Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
• [54] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.