RMC6236 manufacturers
- RMC6236
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- $1.00
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2026-09-14
- CAS:2765081-21-6
- Min. Order: 1g
- Purity: 99
- Supply Ability: 15kg
- Daraxonrasib
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- $52.00
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2026-07-27
- CAS:2765081-21-6
- Purity: 99.66%
- Supply Ability: 10g
- RMC6236
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-
2026-06-30
- CAS:2765081-21-6
- Min. Order: 1kg
- Purity: 98%
- Supply Ability: 1000kg
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| | RMC6236 Basic information |
| Product Name: | RMC6236 | | Synonyms: | RMC6236;(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;(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 , RMC-6236;(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;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]-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)-;"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 | | CAS: | 2765081-21-6 | | MF: | C44H58N8O5S | | MW: | 811.05 | | EINECS: | | | Product Categories: | | | Mol File: | 2765081-21-6.mol |  |
| | RMC6236 Chemical Properties |
| 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 Usage And Synthesis |
| 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]. | | Synthesis | The synthesis of RMC-6236 starts from 3-bromo-5-iodo-2-[(1S)-1-methoxyethyl]pyridine and benzylpiperazine-1-carboxylate, involving palladium-catalyzed couplings, borylation, Suzuki couplings to introduce indole and thiazole moieties, followed by macrocyclization and deprotection steps, and final amidation with (1S,2S)-2-methylcyclopropane-1-carboxylic acid. Key steps include: borylation of T1 to give T2 (crude); Suzuki coupling giving T3 in 48.1% yield; separation of two atropisomers from T5 (A: 36%, B: 34%); borylation of T6 in 76.0% yield; coupling to T7 in 50.9% yield; hydrolysis to T8 in 84.5% yield; macrocyclization to T9 in 54.8% yield; Cbz removal to T10 in 90.4% yield; methylation to T11 in 58.01% yield; final product RMC-6236 in 22.0% yield and 96.4% purity [4].
 | | 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
[4]
Jiang, J., Jiang, L., Maldonato, B. J., et al. (2024). Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discovery, 14(6), 994–1017. https://doi.org/10.1158/2159-8290.cd-24-0027
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| | RMC6236 Preparation Products And Raw materials |
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