Details of the Drug

General Information of Drug (ID: DMM5N8P)

Drug Name

MRX-2843

Synonyms

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; UNC2371A; SCHEMBL14854108; SCHEMBL17175579; BDBM350861; BCP30180; BDBM50055490; MFCD28502224; ZINC299829706; CS-8117; SB17283; AS-35252; HY-101549; US9795606, B20; A16958; UNC2371;UNC-2371;UNC 2371;MRX 2843 ;MRX2843; Cyclohexanol, 4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methyl-1-piperazinyl)methyl)phenyl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)-, trans-; 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; trans-4-(2-((2-Cyclopropylethyl)amino)-5-(4-((4-methyl-1-piperazinyl)methyl)phenyl)-7H-pyrrolo(2,3-d)pyrimidin-7-yl)cyclohexanol

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

488.7

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

8

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

6

Chemical Identifiers

Formula: C29H40N6O
IUPAC Name: 4-[2-(2-cyclopropylethylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol
Canonical SMILES: 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

Cross-matching ID

PubChem CID: 89495685
CAS Number: 89495685
TTD ID: D10LNV

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	[2]
Tyrosine-protein kinase Mer (MERTK)	TTO7LKR	MERTK_HUMAN	Inhibitor	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase Mer (MERTK)	DTT	MERTK	5.86E-04	0.3	0.47
Fms-like tyrosine kinase 3 (FLT-3)	DTT	FLT3	2.11E-01	-0.05	-0.16

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03510104) Pharmacokinetic and Safety Study of MRX-2843 in Adults With Relapsed/Refractory Advanced and/or Metastatic Solid Tumors. U.S. National Institutes of Health.
2	The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630.
3	MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
4	Clinical pipeline report, company report or official report of Ono Pharmaceutical.
5	National Cancer Institute Drug Dictionary (drug name RXDX106).
6	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	National Cancer Institute Drug Dictionary (drug name PF-07265807).
8	A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. Front Oncol. 2020 Dec 7;10:598477.
9	The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature. 2014 Mar 27;507(7493):508-12.
10	G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19.
11	MerTK as a therapeutic target in glioblastoma. Neuro Oncol. 2018 Jan 10;20(1):92-102.
12	UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Mol Cancer Ther. 2013 Nov;12(11):2367-77.
13	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).
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
15	2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
16	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.
17	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
18	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
19	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.
20	Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.