WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 207083
CAS#: 1429882-07-4
Description: MRX-2843, also known as UNC2371, is a potent and orally active MERTK and FLT3 inhibitor. MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. MRX-2843 in combination with an irreversible EGFR TKI as a novel strategy for treatment of patients with wtEGFR NSCLC. 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.
MedKoo Cat#: 207083
Name: MRX-2843
CAS#: 1429882-07-4
Chemical Formula: C29H40N6O
Exact Mass: 488.3264
Molecular Weight: 488.68
Elemental Analysis: C, 71.28; H, 8.25; N, 17.20; O, 3.27
Related CAS #: 1429882-07-4
Synonym: MRX-2843; MRX 2843; MRX2843; UNC2371; UNC-2371; UNC 2371; UNC2371A; UNC-2371A; UNC 2371A;
IUPAC/Chemical Name: (1r,4r)-4-(2-((2-cyclopropylethyl)amino)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanol
InChi Key: LBEJYFVJIPQSNX-SOAUALDESA-N
InChi Code: 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)/t24-,25-
SMILES Code: O[C@H]1CC[C@H](N2C=C(C3=CC=C(CN4CCN(C)CC4)C=C3)C5=CN=C(NCCC6CC6)N=C52)CC1
Appearance: Solid powder
Purity: >95% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | MRX-2843 (UNC2371) is an orally active, ATP-competitive dual MERTK and FLT3 tyrosine kinases inhibitor (TKI) with enzymatic IC50s of 1.3 nM for MERTK and 0.64 nM for FLT3. |
| In vitro activity: | Indeed, treatment with MRX-2843, a first-in-class MERTK kinase inhibitor, resensitized GAS6-treated NSCLC cells to OSI. Functionally, OSIR cells were more sensitive to MRX-2843 than parental cells, suggesting acquired dependence on MERTK signaling. Reference: J Clin Invest. 2022 Aug 1;132(15):e150517. https://pubmed.ncbi.nlm.nih.gov/35708914/ |
| In vivo activity: | A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated therapeutic anti-leukemia effects in immunocompromised mice bearing a MERTK-expressing human leukemia xenograft. In addition, inhibition of host MERTK by genetic deletion (Mertk-/- mice) or treatment with MRX-2843 significantly decreased tumor burden and prolonged survival in immune-competent mice inoculated with a MERTK-negative ALL, suggesting immune-mediated therapeutic activity. Reference: JCI Insight. 2018 Nov 2;3(21):e97941. https://pubmed.ncbi.nlm.nih.gov/30385715/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 34.5 | 70.6 | |
| Ethanol | 25.0 | 51.16 |
The following data is based on the product molecular weight 488.68 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Yan D, Huelse JM, Kireev D, Tan Z, Chen L, Goyal S, Wang X, Frye SV, Behera M, Schneider F, Ramalingam SS, Owonikoko T, Earp HS, DeRyckere D, Graham DK. MERTK activation drives osimertinib resistance in EGFR-mutant non-small cell lung cancer. J Clin Invest. 2022 Aug 1;132(15):e150517. doi: 10.1172/JCI150517. PMID: 35708914; PMCID: PMC9337831. 2. Minson KA, Smith CC, DeRyckere D, Libbrecht C, Lee-Sherick AB, Huey MG, Lasater EA, Kirkpatrick GD, Stashko MA, Zhang W, Jordan CT, Kireev D, Wang X, Frye SV, Earp HS, Shah NP, Graham DK. The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630. doi: 10.1172/jci.insight.85630. PMID: 27158668; PMCID: PMC4855528. 3. Su YT, Butler M, Zhang M, Zhang W, Song H, Hwang L, Tran AD, Bash RE, Schorzman AN, Pang Y, Yu G, Zamboni WC, Wang X, Frye SV, Miller CR, Maric D, Terabe M, Gilbert MR, Earp Iii HS, Wu J. MerTK inhibition decreases immune suppressive glioblastoma-associated macrophages and neoangiogenesis in glioblastoma microenvironment. Neurooncol Adv. 2020 Jun 3;2(1):vdaa065. doi: 10.1093/noajnl/vdaa065. PMID: 32642716; PMCID: PMC7324055. 4. Lee-Sherick AB, Jacobsen KM, Henry CJ, Huey MG, Parker RE, Page LS, Hill AA, Wang X, Frye SV, Earp HS, Jordan CT, DeRyckere D, Graham DK. MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity. JCI Insight. 2018 Nov 2;3(21):e97941. doi: 10.1172/jci.insight.97941. Erratum in: JCI Insight. 2020 Dec 3;5(23): PMID: 30385715; PMCID: PMC6238750. |
| In vitro protocol: | 1. Yan D, Huelse JM, Kireev D, Tan Z, Chen L, Goyal S, Wang X, Frye SV, Behera M, Schneider F, Ramalingam SS, Owonikoko T, Earp HS, DeRyckere D, Graham DK. MERTK activation drives osimertinib resistance in EGFR-mutant non-small cell lung cancer. J Clin Invest. 2022 Aug 1;132(15):e150517. doi: 10.1172/JCI150517. PMID: 35708914; PMCID: PMC9337831. 2. Minson KA, Smith CC, DeRyckere D, Libbrecht C, Lee-Sherick AB, Huey MG, Lasater EA, Kirkpatrick GD, Stashko MA, Zhang W, Jordan CT, Kireev D, Wang X, Frye SV, Earp HS, Shah NP, Graham DK. The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630. doi: 10.1172/jci.insight.85630. PMID: 27158668; PMCID: PMC4855528. |
| In vivo protocol: | 1. Su YT, Butler M, Zhang M, Zhang W, Song H, Hwang L, Tran AD, Bash RE, Schorzman AN, Pang Y, Yu G, Zamboni WC, Wang X, Frye SV, Miller CR, Maric D, Terabe M, Gilbert MR, Earp Iii HS, Wu J. MerTK inhibition decreases immune suppressive glioblastoma-associated macrophages and neoangiogenesis in glioblastoma microenvironment. Neurooncol Adv. 2020 Jun 3;2(1):vdaa065. doi: 10.1093/noajnl/vdaa065. PMID: 32642716; PMCID: PMC7324055. 2. Lee-Sherick AB, Jacobsen KM, Henry CJ, Huey MG, Parker RE, Page LS, Hill AA, Wang X, Frye SV, Earp HS, Jordan CT, DeRyckere D, Graham DK. MERTK inhibition alters the PD-1 axis and promotes anti-leukemia immunity. JCI Insight. 2018 Nov 2;3(21):e97941. doi: 10.1172/jci.insight.97941. Erratum in: JCI Insight. 2020 Dec 3;5(23): PMID: 30385715; PMCID: PMC6238750. |
3: Minson KA, Smith CC, DeRyckere D, Libbrecht C, Lee-Sherick AB, Huey MG, Lasater EA, Kirkpatrick GD, Stashko MA, Zhang W, Jordan CT, Kireev D, Wang X, Frye SV, Earp HS, Shah NP, Graham DK. The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016
Mar;1(3):e85630. doi: 10.1172/jci.insight.85630. PubMed PMID: 27158668; PubMed Central PMCID: PMC4855528.
