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

General Information of Drug (ID: DMTSEXB)

• Drug Name: Bis-(5-hydroxy-1H-indol-2-yl)-methanone Drug Info
• Synonyms: Flt-3 Inhibitor II; 896138-40-2; CHEMBL377193; Bis-(5-hydroxy-1H-indol-2-yl)methanone; Bis(5-hydroxy-1H-indol-2-yl)methanone; SCHEMBL2230377; GTPL5971; CTK8F1061; DTXSID40469293; HMS3229E09; IN1480; BDBM50187351; AKOS028113701; CCG-206752; RT-012728; Flt-3 inhibitor II

Indication

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

• Cross-matching ID:
  PubChem CID: 11601743
  CAS Number: CAS 896138-40-2
  TTD Drug ID: DMTSEXB

Molecule-Related Drug Atlas

Drug(s) Targeting Platelet-derived growth factor receptor alpha (PDGFRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[2]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[3]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[4]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[5]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[6]
CP-868596	DMZIM37	Gastrointestinal cancer	2C11	Phase 3	[7]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[10]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[11]

Drug(s) Targeting Tyrosine-protein kinase Kit (KIT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[13]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[14]
Regorafenib	DMHSY1I	Gastrointestinal stromal tumour	2B5B	Approved	[15]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Pazopanib HCl	DM6U9CQ	Renal cell carcinoma	2C90	Approved	[16]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[17]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[3]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]

Drug(s) Targeting Platelet-derived growth factor receptor beta (PDGFRB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[13]
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[2]
Becaplermin	DM1R5X4	Diabetic complication	5A2Y	Approved	[18]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[6]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
MK-2461	DM21WBH	Alzheimer disease	8A20	Phase 1/2	[19]
SNN-0031	DM2X3BR	Brain injury	NA07.Z	Phase 1/2	[20]
TAK-593	DMNFZOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[22]

Drug(s) Targeting Tyrosine-protein kinase ABL1 (ABL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Bosutinib	DMTI8YE	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[12]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[23]
Adenosine triphosphate	DM79F6G	Malnutrition	5B50-5B71	Approved	[24]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[25]
Flumatinib	DM0G5O6	Chronic myelogenous leukaemia	2A20.0	Phase 2	[26]
DCC-2036	DMJKFNU	Chronic myeloid leukaemia	2A20	Phase 1/2	[27]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[28]
KW-2449	DMFO7RP	Acute myeloid leukaemia	2A60	Phase 1	[29]
IkT-148009	DMMJ9HY	Parkinson disease	8A00.0	Phase 1	[30]

Drug(s) Targeting Fms-like tyrosine kinase 3 (FLT-3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[31]
Ponatinib	DMYGJQO	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Intedanib	DMSTA36	Colorectal cancer	2B91.Z	Approved	[32]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[12]
Gilteritinib	DMTI0ZO	Acute myeloid leukaemia	2A60	Approved	[33]
Pexidartinib	DMS2J0Z	Tenosynovial giant cell tumour	2F7B	Approved	[17]
Pacritinib	DM1T6ZN	Myelofibrosis	2A20.2	Approved	[31]
Quizartinib	DM8Y4JS	Acute myeloid leukaemia	2A60	Approved	[34]
Lestaurtinib	DMQ2AIJ	Acute myeloid leukaemia	2A60	Approved (orphan drug)	[35]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[8]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fms-like tyrosine kinase 3 (FLT-3)	TTGJCWZ	FLT3_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor alpha (PDGFRA)	TT8FYO9	PGFRA_HUMAN	Inhibitor	[1]
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Inhibitor	[1]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[1]

References

• [1] Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. J Med Chem. 2006 Jun 1;49(11):3101-15.
• [2] Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [4] A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [6] E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
• [7] The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
• [8] Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
• [9] National Cancer Institute Drug Dictionary (drug id 452042).
• [10] Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
• [11] Clinical pipeline report, company report or official report of MedImmune (2011).
• [12] 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.
• [13] Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
• [14] New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [16] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [18] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [19] MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
• [20] Company report (Neuronova)
• [21] Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51.
• [22] RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
• [23] 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.
• [24] Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
• [25] Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
• [26] Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
• [27] Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
• [28] Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
• [29] KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
• [30] The c-Abl inhibitor IkT-148009 suppresses neurodegeneration in mouse models of heritable and sporadic Parkinson's disease. Sci Transl Med. 2023 Jan 18;15(679):eabp9352.
• [31] 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: 1807).
• [32] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [33] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [34] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [35] Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with ... Blood. 2008 Jun 15;111(12):5663-71.