 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C29H28CLN7O |
| Exact Mass | 525.2 |
| Elemental Analysis | C, 66.22; H, 5.37; Cl, 6.74; N, 18.64; O, 3.04 |
| CAS # | 2653994-08-0 |
| Related CAS # | (S)-JDQ-443;2653994-10-4 |
| PubChem CID | 156501355 |
| Appearance | White to off-white solid powder |
| LogP | 4.6 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 38 |
| Complexity | 936 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | AZUYLZMQTIKGSC-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C29H28ClN7O/c1-5-24(38)36-14-29(15-36)10-20(11-29)37-17(3)25(26-21-13-31-33-22(21)8-16(2)27(26)30)28(34-37)18-6-7-23-19(9-18)12-32-35(23)4/h5-9,12-13,20H,1,10-11,14-15H2,2-4H3,(H,31,33) |
| Chemical Name | 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one |
| Synonyms | Opnurasib; JDQ-443; JDQ443; JDQ 443; NVP-JDQ443; NVP JDQ443; NVPJDQ443 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | KRAS(G12C) (IC50 = 0.012 μM) |
| ln Vitro |
Opnurasib (NVP-JDQ443) inhibits KRAS's GDP-bound inactive conformation[1]. Opnurasib, with IC50 values of 0.018 and 0.063 μM, respectively, promotes the proliferation of the KRASG12C-mutated cell lines NCI-H358 and NCI-H2122, as well as dose-dependent reductions of phosphorylated ERK (pERK) levels[2]. Opnurasib inhibits GDP-bound KRASG12C with low reversible binding affinity to the RAS switch II pocket in a covalent and selective manner. It also prevents the growth of cell lines that are double-mutant for KRAS and KRASG12C, as well as G12C/H95, G12C/R68S, and G12C/Y96[2]. |
| ln Vivo |
Opnurasib (10-100 mg/kg, Orally, daily for 14 days) exhibits antitumor activity in KRAS G12C-mutated CDX models[2]. Opnurasib (Orally, 100 mg/kg, daily (JDQ443) + 7.5 mg/kg, twice daily (TNO155), for 36 days) exhibits higher cell growth inhibition or cell killing than does single-agent JDQ443 when combined with TNO155[2]. In PDX models of colorectal tumors and non-small cell lung cancer, opracitasin produces distinct antitumor responses that are enhanced by concurrent treatment with additional agents[2]. |
| Cell Assay |
Cell Line: Ba/F3 cells Concentration: 0, 0.3, 1 μM Incubation Time: 30 min, 4 h Result: Inhibited signaling (pERK) and proliferation of the KRAS G12C/H95 double mutants G12C/H95R and G12C/H95Q. |
| Animal Protocol |
KRAS G12C tumor-bearing nude mice (MIA PaCa-2 (PDAC); NCIH2122, LU99, HCC44, NCI-H2030 (NSCLC); and KYSE410 (esophageal cancer)) 10, 30, 100 mg/kg Orally, daily for 14 days |
| References |
[1]. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1. [2]. Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent and Selective, Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022;candisc.0158.2022. |
| Additional Infomation |
Opnurasib is an inhibitor of the oncogenic KRAS substitution mutation, G12C, with potential antineoplastic activity. Upon administration, opnurasib selectively targets the KRAS G12C mutant and inhibits KRAS G12C mutant-dependent signaling. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell growth, proliferation, invasion, and metastasis. Drug Indication Treatment of lung cancer (small cell and non-small cell lung cancer ) |
Solubility Data
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~190.1 mM) Ethanol: ~100 mg/mL (~190.1 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |