Synonym
RMC-4998; RMC 4998; RMC4998;
IUPAC/Chemical Name
(2S)-2-((S)-7-(4-(dimethylamino)-4-methylpent-2-ynoyl)-1-oxo-2,7-diazaspiro[4.4]nonan-2-yl)-N-((63S,4S)-11-ethyl-12-(2-((S)-1-methoxyethyl)pyridin-3-yl)-10,10-dimethyl-5,7-dioxo-61,62,63,64,65,66-hexahydro-11H-8-oxa-1(5,3)-indola-6(1,3)-pyridazina-2(1,3)-benzenacycloundecaphane-4-yl)-3-methylbutanamide
InChi Key
VYZILERTWJIGRC-DOESOIHZSA-N
InChi Code
InChI=1S/C57H74N8O7/c1-12-63-46-21-20-40-32-42(46)43(50(63)41-18-14-26-58-48(41)37(4)71-11)33-55(5,6)35-72-53(69)44-19-15-27-65(60-44)52(68)45(31-38-16-13-17-39(40)30-38)59-51(67)49(36(2)3)64-29-25-57(54(64)70)24-28-62(34-57)47(66)22-23-56(7,8)61(9)10/h13-14,16-18,20-21,26,30,32,36-37,44-45,49,60H,12,15,19,24-25,27-29,31,33-35H2,1-11H3,(H,59,67)/t37-,44-,45-,49-,57-/m0/s1
SMILES Code
O=C(N1CCC[C@@H](C2=O)N1)[C@@H](NC([C@H](C(C)C)N3C([C@@]4(CCN(C(C#CC(C)(C)N(C)C)=O)C4)CC3)=O)=O)CC5=CC(C6=CC(C(CC(C)(C)CO2)=[C@@]([C@@]7=C([C@H](C)OC)N=CC=C7)N8CC)=C8C=C6)=CC=C5
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
Biological target:
KRASG12C inhibitor
In vivo activity:
Disease progression in vivo can also occur due to adaptive mechanisms and increased KRAS-GTP loading. Using the preclinical tool tri-complex KRASG12C-selective covalent inhibitor, RMC-4998 (also known as RM-029), that targets the active GTP-bound (ON) state of the oncogene, we provide a proof-of-concept that the clinical stage KRASG12C(ON) inhibitor RMC-6291 alone or in combination with KRASG12C(OFF) drugs can be an alternative potential therapeutic strategy to circumvent resistance due to increased KRAS-GTP loading.
Reference:
Nokin MJ, Mira A, Patrucco E, Ricciuti B, Cousin S, Soubeyran I, San José S, Peirone S, Caizzi L, Vietti Michelina S, Bourdon A, Wang X, Alvarez-Villanueva D, Martínez-Iniesta M, Vidal A, Rodrigues T, García-Macías C, Awad MM, Nadal E, Villanueva A, Italiano A, Cereda M, Santamaría D, Ambrogio C. RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade. Nat Commun. 2024 Aug 30;15(1):7554. doi: 10.1038/s41467-024-51828-2. PMID: 39215000; PMCID: PMC11364849.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
983.27
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 |
1: Nokin MJ, Mira A, Patrucco E, Ricciuti B, Cousin S, Soubeyran I, San José S,
Peirone S, Caizzi L, Vietti Michelina S, Bourdon A, Wang X, Alvarez-Villanueva
D, Martínez-Iniesta M, Vidal A, Rodrigues T, García-Macías C, Awad MM, Nadal E,
Villanueva A, Italiano A, Cereda M, Santamaría D, Ambrogio C. RAS-ON inhibition
overcomes clinical resistance to KRAS G12C-OFF covalent blockade. Nat Commun.
2024 Aug 30;15(1):7554. doi: 10.1038/s41467-024-51828-2. PMID: 39215000; PMCID:
PMC11364849.
2: Anastasiou P, Moore C, Rana S, Tomaschko M, Pillsbury CE, de Castro A,
Boumelha J, Mugarza E, de Carné Trécesson S, Mikolajczak A, Blaj C, Goldstone R,
Smith JAM, Quintana E, Molina-Arcas M, Downward J. Combining RAS(ON)
G12C-selective inhibitor with SHP2 inhibition sensitises lung tumours to immune
checkpoint blockade. Nat Commun. 2024 Sep 25;15(1):8146. doi:
10.1038/s41467-024-52324-3. PMID: 39322643; PMCID: PMC11424635.
