| Size | Price | Stock | Qty |
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| 1mg |
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| 2mg |
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| 5mg |
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| 25mg |
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Purity: ≥98%
MRTX-1257 is a novel, potent, selective, orally bioavailable and covalent / irreversible inhibitor of KRAS G12C with an IC50 of 900 pM for KRAS dependent ERK phosphorylation in H358 cells. With free fraction exposures well above the cellular potency, MRTX1257 showed a 31% bioavailability in mice. 77% of the experiment's PK/PD targets engagement.
| Targets |
KRAS G12C; KRAS(G12C) (IC50 = 900 pM)
|
|---|---|
| ln Vitro |
MRTX1257 demonstrates rapid, irreversible modification of GDP-bound recombinant KRAS G12C and suppresses ERK phosphorylation with an IC50 = 1 nM in the H358 cell line. MRTX1257 is shown to be highly selective for the targeted Cys12 of KRAS G12C compared to other surface-exposed cysteine residues in NCI-H358 cells in proteomics studies intended to assess global protein modification.[2]
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| ln Vivo |
MRTX1257 has a 31% bioavailability in mice, exhibits nearly complete KRAS signaling inhibition in tumor tissue, and completely eradicates durable tumor regression in MIA PaCa-2 xenografts.[2]
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| Animal Protocol |
mice
3 mg/kg, 30 mg/kg IV, Oral gavage |
| References |
| Molecular Formula |
C33H39N7O2
|
|---|---|
| Molecular Weight |
565.708466768265
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| Exact Mass |
565.72
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| Elemental Analysis |
C, 70.06; H, 6.95; N, 17.33; O, 5.66
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| CAS # |
2206736-04-9
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| Related CAS # |
MRTX-1257-d6;2639608-44-7
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| PubChem CID |
134326084
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| Appearance |
Off-white to pink solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
42
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C2C(=CC=C1)C=CC=C2N3CCC4=C(C3)N=C(N=C4N5CCN([C@H](C5)CC#N)C(=O)C=C)OC[C@@H]6CCCN6C
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| InChi Key |
YRYQLVCTQFBRLD-UIOOFZCWSA-N
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| InChi Code |
InChI=1S/C33H39N7O2/c1-4-30(41)40-19-18-39(20-25(40)13-15-34)32-27-14-17-38(29-12-6-10-24-9-5-8-23(2)31(24)29)21-28(27)35-33(36-32)42-22-26-11-7-16-37(26)3/h4-6,8-10,12,25-26H,1,7,11,13-14,16-22H2,2-3H3/t25-,26-/m0/s1
|
| Chemical Name |
2-[(2S)-4-[7-(8-methylnaphthalen-1-yl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-prop-2-enoylpiperazin-2-yl]acetonitrile
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| Synonyms |
MRTX-1257; MRTX1257; MRTX 1257
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~176.8 mM)
Ethanol: ~30 mg/mL (~53.0 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.42 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 25.0 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: 2.5 mg/mL (4.42 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7677 mL | 8.8385 mL | 17.6769 mL | |
| 5 mM | 0.3535 mL | 1.7677 mL | 3.5354 mL | |
| 10 mM | 0.1768 mL | 0.8838 mL | 1.7677 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
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