Drug Information

Drug (ID: DG01639) and It's Reported Resistant Information

• Name: MRX-2843
• Synonyms: MRX-2843; 1429882-07-4; UNC-2371A; UNII-2MT30EHI63; 2MT30EHI63; CHEMBL3326007; (1r,4r)-4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol; Cyclohexanol, 4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methyl-1-piperazinyl)methyl)phenyl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-, trans-; trans-4-(2-((2-Cyclopropylethyl)amino)-5-(4-((4-methyl-1-piperazinyl)methyl)phenyl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)cyclohexanol; UNC2371A; SCHEMBL14854108; SCHEMBL17175579; UNC2371UNC2371; BDBM350861; BCP30180; BDBM50055490; MFCD28502224; s6839; ZINC299829706; CS-8117; SB17283; AS-35252; HY-101549; MRX-2843; (UNC-2371A); US9795606, B20; A16958; UNC2371;UNC-2371;UNC 2371;MRX 2843 ;MRX2843; 4-[2-(2-cyclopropylethylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol; trans-(1R,4R)-4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol
• Indication:
  In total 3 Indication(s)
  Bladder cancer [ICD-11: 2C94]; Phase 1; [1]
  Cholangiocarcinoma [ICD-11: 2C12]; Phase 1; [1]
  Myeloproliferative syndrome [ICD-11: 2A20]; Phase 1; [1]
• Target: Fibroblast growth factor receptor 1 (FGFR1); FGFR1_HUMAN; [1]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [1]
• Target: Fibroblast growth factor receptor 3 (FGFR3); FGFR3_HUMAN; [1]
• Formula: 8
• IsoSMILES: CN1CCN(CC1)CC2=CC=C(C=C2)C3=CN(C4=NC(=NC=C34)NCCC5CC5)C6CCC(CC6)O
• InChI: InChI=1S/C29H40N6O/c1-33-14-16-34(17-15-33)19-22-4-6-23(7-5-22)27-20-35(24-8-10-25(36)11-9-24)28-26(27)18-31-29(32-28)30-13-12-21-2-3-21/h4-7,18,20-21,24-25,36H,2-3,8-17,19H2,1H3,(H,30,31,32)
• InChIKey: LBEJYFVJIPQSNX-UHFFFAOYSA-N
• PubChem CID: 89495685
• TTD Drug ID: D0O6UY

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]

• Molecule Alteration: Missense mutation; p.D835V (c.2504A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: NOMO-1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells.

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]

• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: MOLM-14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: NOMO-1 cells; Bone marrow; Homo sapiens (Human); CVCL_1609
• In Vivo Model: NSG mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: FACS assay
• Mechanism Description: MRX-2843, a type 1 small-molecule tyrosine kinase inhibitor that abrogates activation of both MERTK and FLT3 and their downstream effectors. MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD, with a wide therapeutic window compared with that of normal human cord blood cells.

References

• Ref 1: The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemiaJCI Insight. 2016 Mar;1(3):e85630. doi: 10.1172/jci.insight.85630.