RMC6236
- CAS No.
- 2765081-21-6
- Chemical Name:
- RMC6236
- Synonyms
- RMC6236;Daraxonrasib;RMC-6236 RASONMULTI;"Cyclopropanecarboxamide, N-[(2R,14S,18S)-1-ethyl-18, 19,20,21-tetrahydro-2-[2-[(1S)-1-methoxyethyl]-5-(4-methyl-1-piperazinyl)-3-pyridinyl]-2";(1S,2S)-N-((63S,4S,Z)-11-ethyl-12-(2-((S)-1-methoxyethyl)-5-(4-methylpiperazin-1-yl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-thiazola-1(5,3)-indola-6(1,3)-py;(Z)-N-(11-ethyl-12-(2-(1-methoxyethyl)-5-(4-methylpiperazin-1-yl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-thiazola-1(5,3)-indola-6(1,3)-pyridazinacycloundecaphane-4-yl)-2-methylcyclopropane-1-carboxamide;N-[21-ethyl-20-[2-(1-methoxyethyl)-5-(4-methylpiperazin-1-yl)pyridin-3-yl]-17,17-dimethyl-8,14-dioxo-15-oxa-4-thia-9,21,27,28-tetrazapentacyclo[17.5.2.12,5.19,13.022,26]octacosa-1(25),2,5(28),19,22(26),23-hexaen-7-yl]-2-methylcyclopropane-1-carboxamide;(1S,2S)-N-((63S,4S,Z)-11-ethyl-12-(2-((S)-1-methoxyethyl)-5-(4-methylpiperazin-1-yl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-thiazola-1(5,3)-indola-6(1,3)-pyridazinacycloundecaphane-4-yl)-2-methylcyclopropane-1-carboxamide;(1S,2S)-N-[(2R,14S,18S)-1-Ethyl-18,19,20,21-tetrahydro-2-[2-[(1S)-1-methoxyethyl]-5-(4-methyl-1-piperazinyl)-3-pyridinyl]-25,25-dimethyl-15,22-dioxo-17H-5,3-([4,2]-endo-thiazolopropano[1,3]-endo-pyridazinomethanoxypropano)-1H-indol-14-yl]-2-methyl-cyclopropanecarboxamide;Cyclopropanecarboxamide, N-[(2R,14S,18S)-1-ethyl-18,19,20,21-tetrahydro-2-[2-[(1S)-1-methoxyethyl]-5-(4-methyl-1-piperazinyl)-3-pyridinyl]-25,25-dimethyl-15,22-dioxo-17H-5,3-([4,2]-endo-thiazolopropano[1,3]-endo-pyridazinomethanoxypropano)-1H-indol-14-yl]-2-methyl-, (1S,2S)-
- CBNumber:
- CB211845498
- Molecular Formula:
- C44H58N8O5S
- Molecular Weight:
- 811.05
- MDL Number:
- MOL File:
- 2765081-21-6.mol
| Density | 1.37±0.1 g/cm3(Predicted) |
|---|---|
| solubility |
DMSO: Sparingly soluble: 1-10 mg/ml Ethanol: Sparingly soluble: 1-10 mg/ml |
| pka | 14.56±0.40(Predicted) |
| form | Solid |
| color | White to off-white |
| InChIKey | FVICRBSEYSHKFY-UHFFFAOYSA-N |
| SMILES | C(N1C2=CC=C3C4=CSC(CC(C(=O)N5CCCC(N5)C(=O)OCC(C)(C)CC(C2=C3)=C1C1C=C(N2CCN(C)CC2)C=NC=1C(C)OC)NC(C1CC1C)=O)=N4)C |
RMC6236 Chemical Properties,Uses,Production
Uses
RMC-6236 is an orally active, non-covalent RAS (ON) inhibitor. RMC-6236 disrupts the interaction of wild-type or mutant RAS proteins with the RAS binding domain of BRAF, with EC50 values ranging from 28-220 nM for wild-type KRAS, NRAS, HRAS, and multiple oncogenic RAS variants. RMC-6236 inhibits pERK. RMC-6236 has anti-tumor activity against KRAS mutant tumors[1][2][3].
in vivo
RMC-6236 (3-25 mg/kg; p.o.; single dose) shows dose-dependent blood and tumor exposure in the Capan-2 xenograft tumor-bearing BALB/c nude mouse model, with tumor exposure approximately 3-7 times higher than that in blood and relatively slower elimination from tumors[1].
RMC-6236 (10-25 mg/kg; p.o.; once daily; 4 weeks) shows dose-dependent antitumor activity in a series of human tumor xenograft models harboring prevalent KRAS mutations (such as Capan-2, NCI-H441, HPAC, NCI-H358, etc.)[1].
RMC-6236 (25 mg/kg; p.o.; once daily) can arrest tumor growth when used alone in xenograft models of KRASG12C-mutant NCI-H2122 non-small cell lung cancer and KRASG12D-mutant GP2D colorectal cancer, and it can lead to significant tumor regression when combined with KO-2806[2].
IC 50
KRas G12D
References
[1] Jiang J, et al. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Jun 3;14(6):994-1017. DOI:10.1158/2159-8290.CD-24-0027
[2] Patel H V, et al. The farnesyl transferase inhibitor KO-2806 re-sensitizes relapsing tumors to RAS inhibition. BioRxiv, 2024: 2024.12. 20.629824.
[3] Long SA, et al. Evaluation of KRAS inhibitor-directed therapies for pancreatic cancer treatment. Front Oncol. 2024 May 10;14:1402128. DOI:10.3389/fonc.2024.1402128
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解释：在groupA和groupB中，groupB里的文献引用与groupA中的第一条文献引用的标题（忽略大小写和标点）和DOI都相同，属于重复引用，根据规则以groupA中的数据为准，所以最终结果只保留groupA中的三条文献引用。
RMC6236 Preparation Products And Raw materials
Raw materials
Preparation Products
RMC6236 Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Suzhou Biosyntech Co., Ltd | +86-13921151340 | sales2@biosyntech-suzhou.com | China | 104 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354; +17819995354 | marketing@targetmol.com | United States | 32432 | 58 |
| Suzhou ARTK Medchem Co., Ltd. | +86-512-68323658 +86-18168183658 | sales1@artkmedchem.com | China | 39002 | 58 |
| Shanghai hope-chem Co.,Ltd | +86-19121697802 19121697802; | info@hope-chem.com | China | 18 | 58 |
| Guangzhou CATO Research Chemicals Inc. | +86-020-81960175-617 +8615602392859 | Intermediate@cato-chem.com | China | 3861 | 58 |
| Shaanxi Dideu New Materials Co. Ltd | +86-18192503167 | 1036@dideu.com | China | 6761 | 58 |
| Shanghai Hanhong Scientific Co., Ltd. | +undefined17612118332 | Lucky@hanhonggroup.com | China | 5844 | 58 |
| Hangzhou Collab Medicine Co.,Ltd. | +8615936229464 | candice@collab-med.com | China | 915 | 58 |
| Chengdu Feibo Pharm Technology Co., Ltd | +86 028-84641798 15982321820 | abby@arkpharm.com | China | 10000 | 58 |
| Jurong Coupling Biotechnology Co., Ltd. | 19231718652 | 278191416@qq.com | China | 420 | 58 |
