WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H207192
CAS#: 2765081-21-6
Description: RMC-6236, also known as RAS-IN-2, is an oral therapeutic drug that inhibits the active state of multiple RAS variants. It targets the KRAS protein, which is made by a mutated gene and sends signals that cause cancer cells to grow. RMC-6236 prevents the KRAS protein from sending these signals, which may slow or stop the growth of cancer cells.
Hodoodo Cat#: H207192
Name: RMC-6236
CAS#: 2765081-21-6
Chemical Formula: C44H58N8O5S
Exact Mass: 810.43
Molecular Weight: 811.060
Elemental Analysis: C, 65.16; H, 7.21; N, 13.82; O, 9.86; S, 3.95
Related CAS #: 2765091-21-0 (racemate) 2765081-21-6
Synonym: RMC-6236; RMC 6236; RMC6236; RAS-IN-2; RAS In 2;
IUPAC/Chemical Name: (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
InChi Key: FVICRBSEYSHKFY-JYQNNKODSA-N
InChi Code: InChI=1S/C44H58N8O5S/c1-8-51-37-12-11-28-19-31(37)33(40(51)32-20-29(23-45-39(32)27(3)56-7)50-16-14-49(6)15-17-50)22-44(4,5)25-57-43(55)34-10-9-13-52(48-34)42(54)35(21-38-46-36(28)24-58-38)47-41(53)30-18-26(30)2/h11-12,19-20,23-24,26-27,30,34-35,48H,8-10,13-18,21-22,25H2,1-7H3,(H,47,53)/t26-,27-,30-,34-,35-/m0/s1
SMILES Code: CC(COC([C@H]1NN(C([C@H](CC2=NC3=CS2)NC([C@H]4C[C@@H]4C)=O)=O)CCC1)=O)(C)CC5=[C@@](N(CC)C6=C5C=C3C=C6)[C@@]7=C([C@H](C)OC)N=CC(N8CCN(C)CC8)=C7
Appearance: To be determined
Purity: >98% (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: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
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
More Info: KRAS is mutated in approximately 30% of cancers, and the most frequent mutations replace the glycine at position 12 (G12) with another amino acid in cancers such as pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC) RAS plays an important role in cell signaling, division and differentiation. Mutations of RAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. (note the structure was from https://www.sohu.com/a/640171704_121124565).
| Biological target: | |
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| In vivo activity: |
The following data is based on the product molecular weight 811.06 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: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, Singh M. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Apr 9:OF1-OF24. doi: 10.1158/2159-8290.CD-24-0027. Epub ahead of print. PMID: 38593348.
2: Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, Patrucco E, Goodhart G, Dilly J, Gindin Y, Dinglasan N, Wang Y, Lai LP, Cai S, Jiang L, Nasholm N, Shifrin N, Blaj C, Shah H, Evans JW, Montazer N, Lai O, Shi J, Ahler E, Quintana E, Chang S, Salvador A, Marquez A, Cregg J, Liu Y, Milin A, Chen A, Ziv TB, Parsons D, Knox JE, Klomp JE, Roth J, Rees M, Ronan M, Cuevas-Navarro A, Hu F, Lito P, Santamaria D, Aguirre AJ, Waters AM, Der CJ, Ambrogio C, Wang Z, Gill AL, Koltun ES, Smith JAM, Wildes D, Singh M. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024 Apr 8. doi: 10.1038/s41586-024-07205-6. Epub ahead of print. PMID: 38589574.
3: Drugging RAS: Moving Beyond KRASG12C. Cancer Discov. 2023 Dec 12;13(12):OF7. doi: 10.1158/2159-8290.CD-ND2023-0010. PMID: 37871268.
