Synonym
RM 036; RM-036; RM036; RMC 9805; RMC-9805; RMC9805; Zoldonrasib
IUPAC/Chemical Name
(2S)-2-cyclopentyl-2-((S)-7-((2R,3R)-3-cyclopropyl-1-methylaziridine-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)-N-((22S,63S,4S)-12-(5-(4-cyclopropylpiperazin-1-yl)-2-((S)-1-methoxyethyl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-11-(2,2,2-trifluoroethyl)-61,62,63,64,65,66-hexahydro-11H-8-oxa-2(4,2)-morpholina-1(5,3)-indola-6(1,3)-pyridazinacycloundecaphane-4-yl)acetamide
InChi Key
VKNNQJWNUPSOEK-QFVODIEJSA-N
InChi Code
InChI=1S/C63H88F3N11O7/c1-39(82-5)52-47(30-44(33-67-52)72-25-23-71(24-26-72)42-14-15-42)55-48-32-61(2,3)38-84-60(81)49-11-8-20-77(69-49)58(79)50(31-45-34-73(27-28-83-45)43-16-17-51(46(48)29-43)76(55)37-63(64,65)66)68-57(78)54(40-9-6-7-10-40)74-21-18-62(35-74)19-22-75(36-62)59(80)56-53(70(56)4)41-12-13-41/h16-17,29-30,33,39-42,45,49-50,53-54,56,69H,6-15,18-28,31-32,34-38H2,1-5H3,(H,68,78)/t39?,45-,49-,50-,53+,54-,56+,62-,70?/m0/s1
SMILES Code
CC(COC([C@H]1NN(C([C@@H](NC([C@H](C2CCCC2)N3C[C@]4(CN(C([C@@H]5N(C)[C@@H]5C6CC6)=O)CC4)CC3)=O)C[C@@H]7OCCN8C7)=O)CCC1)=O)(C)CC9=[C@@](N(CC(F)(F)F)C%10=C9C=C8C=C%10)[C@@]%11=C([C@H](C)OC)N=CC(N(CC%12)CCN%12C%13CC%13)=C%11
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
Zoldonrasib (RMC-9805) is a first-in-class, oral, mutant-selective covalent inhibitor targeting the active GTP-bound KRAS^G12D^ (RAS(ON)) protein. It forms a high-affinity tri-complex with KRAS^G12D^ and cyclophilin A, leading to selective covalent modification of the mutant Asp12 residue, thereby disrupting downstream RAS signaling pathways. In preclinical studies, RMC-9805 demonstrated potent anti-tumor activity, inducing apoptosis and tumor regression in KRAS^G12D^-mutant pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) models. Specifically, it achieved objective responses in 7 of 9 PDAC models and 6 of 9 NSCLC models. In colorectal cancer (CRC) models, which are less dependent on KRAS mutations, combination therapies with RMC-9805 and other RAS pathway inhibitors improved response rates up to 60% and delayed resistance onset. Furthermore, RMC-9805 synergized with anti-PD-1 therapy, enhancing T-cell infiltration and promoting immunological memory in KRAS^G12D^ tumors. Clinically, in a Phase 1/1b trial involving patients with KRAS^G12D^-mutant PDAC, RMC-9805 monotherapy at 1200 mg daily or 600 mg twice daily achieved a 30% objective response rate and 80% disease control rate, with a favorable safety profile characterized by primarily Grade 1 gastrointestinal-related adverse events
