2. GPCR/G Protein MAPK/ERK Pathway
  3. Ras
  4. Divarasib

Divarasib (GDC-6036) is an orally active, selective KRASG12C inhibitor with an IC50 of <0.01 μM. Divarasib covalently binds Cys12 in GDP-bound KRASG12C, occupies the switch II pocket, blocks GTP binding and SOS-mediated reactivation, and inhibits oncogenic KRAS signaling. Divarasib induces tumor shrinkage and robust tumor growth inhibition in KRASG12C-positive models and cancer cells. Divarasib can be used for the research of non-small cell lung cancer, colorectal adenocarcinoma, pancreatic ductal adenocarcinoma, and other KRASG12C-mutated solid tumors.

For research use only. We do not sell to patients.

CAS No. : 2417987-45-0

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10 mM * 1 mL in DMSO
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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of Divarasib:

Divarasib Related Antibodies

Top Publications Citing Use of Products

    Divarasib purchased from MedChemExpress. Usage Cited in: Ann Oncol. 2025 Jun;36(6):682-692.

    Divarasib exhibited a half-maximal inhibitory concentration (IC50) of 0.19 nmol/L in the MIA PaCa‑2 cell line harboring only the single KRASG12C mutation.

    Divarasib purchased from MedChemExpress. Usage Cited in: Cell. 2024 Oct 31;187(22):6379-6392.e17.  [Abstract]

    IP of active GTP-bound Rap1 using GST-RalGDS-RBD of HeLa cells transiently overexpressing EGFP-Rap1A(WT) and EGFP-Rap1A(G12C, L96F) and treated with different concentrations of Divarasib (10-50 μM; 12 h). The results showed that treatment with Divarasib effectively inhibited the activity of Rap1A(G12C, L96F).

    Divarasib purchased from MedChemExpress. Usage Cited in: Cell. 2024 Oct 31;187(22):6379-6392.e17.  [Abstract]

    Relative growth of MOLM-13-KRAS-G12C, MOLM-13-NRAS-G12C, and MOLM-13-KRAS-G12D cells after treatment with K-Ras(G12C) inhibitors (Divarasib et al.) for 72 h.

    Divarasib purchased from MedChemExpress. Usage Cited in: Cell. 2024 Oct 31;187(22):6379-6392.e17.  [Abstract]

    Surface plasmon resonance experiment with Divarasib and RalA(WT), Rap1A(WT), and RhoA(WT). The results showed that Divarasib bound reversely to both RalA(WT) and Rap1A(WT), whereas no binding to RhoA(WT) was detected.

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    K-Ras H-Ras N-Ras Ras

    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Divarasib (GDC-6036) is an orally active, selective KRASG12C inhibitor with an IC50 of <0.01 μM. Divarasib covalently binds Cys12 in GDP-bound KRASG12C, occupies the switch II pocket, blocks GTP binding and SOS-mediated reactivation, and inhibits oncogenic KRAS signaling. Divarasib induces tumor shrinkage and robust tumor growth inhibition in KRASG12C-positive models and cancer cells. Divarasib can be used for the research of non-small cell lung cancer, colorectal adenocarcinoma, pancreatic ductal adenocarcinoma, and other KRASG12C-mutated solid tumors[1][2][3][4].

    IC50 & Target[1]

    K-Ras(G12C)

    <0.01 μM (IC50)

    In Vitro

    Divarasib (20 μM; overnight at room temperature) covalently binds to purified KRASG12C protein with complete or near-complete alkylation[1].
    Divarasib (18 h) potently inhibits SOS-mediated nucleotide exchange on purified KRASG12C protein with an IC50 of 0.0024 nM[2].
    Divarasib (18 h) covalently alkylates KRASG12C in 2D-cultured HCC1171 cells with an IC50 of 2.2 nM[2].
    Divarasib (18 h) covalently alkylates KRASG12C in 3D-cultured HCC1171 cells with an IC50 of 0.42 nM, reflecting more accurate target engagement potency in 3D culture[2].
    Divarasib (7 days) potently inhibits viability across a panel of KRASG12C-positive cell lines with a geometric mean IC50 of 0.56 nM, and exhibits 9200-fold selectivity over non-KRASG12C cell lines[2].
    Divarasib (10 nM; 4 h) shows high selective reactivity for KRASG12C cysteine over more than 11,000 other reactive cysteines in HCC1171 cells[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Divarasib Related Antibodies
    Parmacokinetics
    Species Dose Route CLplasma Vss T1/2 F
    Mice[2] 1 mg/kg i.v. 24 mL/min/kg 2.0 L/kg 1.4 h /
    Mice[2] 3 mg/kg p.o. / / 1.4 h 17 %
    Rat[2] 1 mg/kg i.v. 69 mL/min/kg 5.4 L/kg 1.4 h /
    Rat[2] 3 mg/kg p.o. / / 1.4 h 6 %
    Dog[2] 0.5 mg/kg i.v. 75 mL/min/kg 4.5 L/kg 1.2 h /
    Dog[2] 0.5 mg/kg p.o. / / 1.2 h 25 %
    Cynomolgus Monkey[2] 0.5 mg/kg i.v. 10 mL/min/kg 1.2 L/kg 1.4 h /
    Cynomolgus Monkey[2] 0.5 mg/kg p.o. / / 1.4 h 5 %
    In Vivo

    Divarasib (GDC-6036) (10-100 mg/kg; p.o.; daily; 7 days) induces dose-dependent KRASG12C target engagement in KRASG12C-positive NSCLC xenografts, with over 90% engagement at the 100 mg/kg daily oral dose, which correlates with the greatest tumor shrinkage[1].
    Divarasib (0.1-50 mg/kg; p.o.; daily; 21 days; 0.5-100 mg/kg; p.o.; single dose) induces dose-dependent tumor regression and MAPK pathway suppression in NCI-H358 xenografts, with an ED50 of 2.0 mg/kg for antitumor activity and 6.6 mg/kg for KRASG12C alkylation[2].
    Divarasib (0.7-100 mg/kg; p.o.; daily; 21 days; 5-100 mg/kg; p.o.; single dose) induces dose-dependent tumor stasis and MAPK pathway suppression in NCI-H2122 xenografts, with an ED50 of 6.3 mg/kg for antitumor activity and 9.7 mg/kg for KRASG12C alkylation[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Model: C.B-17 SCID (Inbred) (female, 20−21 weeks old, average weight 24.1 g, subcutaneously implanted with human NSCLC NCI-H2030.X1.1 cells)[1]
    Dosage: 10 mg/kg; 25 mg/kg; 100 mg/kg
    Administration: p.o.; daily; 7 days
    Result: Exhibited dose-dependent KRAS G12C target engagement across 2, 8, and 24 h post-last dose.
    Achieved over 90% KRAS G12C engagement for the 100 mg/kg dose.
    Correlated KRAS G12C engagement with percent change in tumor volume from day 0 to day 7.
    Induced the greatest tumor shrinkage in all animals at the 100 mg/kg dose.
    Animal Model: C.B-17 SCID (Inbred; female)[2]
    Dosage: 0.1-50 mg/kg (daily dosing for antitumor activity); 0.5-100 mg/kg (single dose for PK/PD)
    Administration: p.o.; daily; 21 days; p.o.; single dose
    Result: Drove tumor regression at doses of 5 mg/kg, 15 mg/kg, and 50 mg/kg.
    Achieved tumor stasis at 5 mg/kg, while higher doses reduced tumors below the lower limit of detection.
    Reached an ED50 of 2.0 mg/kg and ED90 of 13 mg/kg for tumor response.
    Achieved ~95% suppression of MAPK target genes DUSP6 and SPRY4 with a single 10 mg/kg dose.
    Achieved ~75% KRAS G12C alkylation and 0.2 nM free drug concentration in plasma with a single 10 mg/kg dose.
    Reached an alkylation ED50 of 6.6 mg/kg.
    Clinical Trial
    Molecular Weight

    622.06

    Formula

    C29H32ClF4N7O2
    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    NC1=N[C@]([C@]2=C(C=C3C(N=C(N=C3N4[C@H](CN(CC4)C(C=C)=O)C)OC[C@H]5N(CCC5)C)=C2F)Cl)=C(C(C)=C1)C(F)(F)F
    Shipping

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (160.76 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.6076 mL 8.0378 mL 16.0756 mL
    5 mM 0.3215 mL 1.6076 mL 3.2151 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (4.02 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.02 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
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    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.31%

    SDS (252 KB)

    COA (252 KB) HNMR (325 KB) RP-HPLC (247 KB) LCMS (94 KB)

    Handling Instructions (2659 KB)
    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.6076 mL 8.0378 mL 16.0756 mL 40.1890 mL
    5 mM 0.3215 mL 1.6076 mL 3.2151 mL 8.0378 mL
    10 mM 0.1608 mL 0.8038 mL 1.6076 mL 4.0189 mL
    15 mM 0.1072 mL 0.5359 mL 1.0717 mL 2.6793 mL
    20 mM 0.0804 mL 0.4019 mL 0.8038 mL 2.0095 mL
    25 mM 0.0643 mL 0.3215 mL 0.6430 mL 1.6076 mL
    30 mM 0.0536 mL 0.2679 mL 0.5359 mL 1.3396 mL
    40 mM 0.0402 mL 0.2009 mL 0.4019 mL 1.0047 mL
    50 mM 0.0322 mL 0.1608 mL 0.3215 mL 0.8038 mL
    60 mM 0.0268 mL 0.1340 mL 0.2679 mL 0.6698 mL
    80 mM 0.0201 mL 0.1005 mL 0.2009 mL 0.5024 mL
    100 mM 0.0161 mL 0.0804 mL 0.1608 mL 0.4019 mL
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    Divarasib Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    Divarasib2417987-45-0GDC-6036GDC6036GDC 6036RasA549 KRAS G12S mouse xenograftGTPpancreatic ductal adenocarcinomaCys12colorectal adenocarcinomanon-small cell lung cancerswitch II pocketKRAS G12CGDP-bound KRAS G12CSOSInhibitorinhibitorinhibit

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