Art. -Nr.: HY-145928

Divarasib

(Synonyms: GDC-6036)

6 Cited Publications

Kundenbewertung

Based on 6 publication(s) in Google Scholar

Divarasib (GDC-6036) is an orally active, selective KRAS^G12C inhibitor with an IC₅₀ of <0.01 μM. Divarasib covalently binds Cys12 in GDP-bound KRAS^G12C, 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 KRAS^G12C-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 KRAS^G12C-mutated solid tumors.

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Reinheit: 99.31%
CAS. Nr.: 2417987-45-0
Formel: C₂₉H₃₂ClF₄N₇O₂
Molecular Weight:622.06

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Divarasib Chemical Structure

CAS. Nr.: 2417987-45-0

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
- Clinical Trial
Chemical Information
Publications (6)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

K-Ras(G12C)

<0.01 μM (IC₅₀)

Alle Ras Isoform-spezifische Produkte anzeigen :

In Vitro

Divarasib (20 μM; overnight at room temperature) covalently binds to purified KRAS^G12C protein with complete or near-complete alkylation^[1].
Divarasib (18 h) potently inhibits SOS-mediated nucleotide exchange on purified KRAS^G12C protein with an IC₅₀ of 0.0024 nM^[2].
Divarasib (18 h) covalently alkylates KRAS^G12C in 2D-cultured HCC1171 cells with an IC₅₀ of 2.2 nM^[2].
Divarasib (18 h) covalently alkylates KRAS^G12C 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 KRAS^G12C-positive cell lines with a geometric mean IC₅₀ of 0.56 nM, and exhibits 9200-fold selectivity over non-KRAS^G12C cell lines^[2].
Divarasib (10 nM; 4 h) shows high selective reactivity for KRAS^G12C 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.

Parmacokinetics

Species	Dose	Route	CL_plasma	V_ss	T_1/2	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 KRAS^G12C target engagement in KRAS^G12C-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 KRAS^G12C 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 KRAS^G12C 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

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 2417987-45-0
Appearance Solid
Molecular Weight 622.06
Formel C₂₉H₃₂ClF₄N₇O₂
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
Synonyms

GDC-6036
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (6)

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Journal Impact Factor

Ann Oncol

Genomic landscape of clinically acquired resistance alterations in patients treated with KRASG12C inhibitors. [Abstract]

2025 Jun;36(6):682-692. PMID: 39914665

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

Divarasib exhibited a half-maximal inhibitory concentration (IC₅₀) of 0.19 nmol/L in the MIA PaCa‑2 cell line harboring only the single KRAS^G12C mutation.
Cell

Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket. [Abstract]

2024 Oct 31;187(22):6379-6392.e17. PMID: 39255801

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.
Cancer Discov

Sotorasib is a pan-RASG12C inhibitor capable of driving clinical response in NRASG12C cancers. [Abstract]

2024 May 1;14(5):727-736. PMID: 38236605
Nat Cancer

The MEK-RAF molecular glue IK-595 has potent antitumor activity across RAS/MAPK pathway-altered cancers. [Abstract]

2026 Jan;7(1):116-130. PMID: 41482524
ACS Omega

Application and Cross-Validation of a High-Throughput SPR Method for Characterizing Covalent Binding Ligands. [Abstract]

2025 Jul 4;10(27):29637-29646. PMID: 40687013
Patent

US20240307395A1.

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.6076 mL

8.0378 mL

16.0756 mL

5 mM

0.3215 mL

1.6076 mL

3.2151 mL

10 mM

0.1608 mL

0.8038 mL

1.6076 mL

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.

Molaritätsrechner

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

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

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

Stock Solution Working Solution

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.

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

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

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

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).

Working solution concentration: 0.22 mg/mL

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (293 KB)
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Meng L, et al. Assessment of KRAS G12C Target Engagement by a Covalent Inhibitor in Tumor Biopsies Using an Ultra-Sensitive Immunoaffinity 2D-LC-MS/MS Approach. Anal Chem. 2022 Sep 20;94(37):12927-12933. [Content Brief]

[2]. Endres NF, et al. Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C. J Med Chem. 2026;69(5):5147-5165. [Content Brief]

[3]. Brazel D, et al. Divarasib in the Evolving Landscape of KRAS G12C Inhibitors for NSCLC. Target Oncol. 2024;19(3):297-301. [Content Brief]

[4]. Jayesh Desai, et al. Abstract CT029: Phase Ib study of GDC-6036 in combination with cetuximab in patients with colorectal cancer (CRC) with KRAS G12C mutation. Cancer Res (2023) 83 (8_Supplement): CT029.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

Divarasib

6 Cited Publications

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Divarasib

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

KRAS Targeted Compound Library

Publications Citing Use of MedChemExpress (MCE) Divarasib

Alle Ras Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Divarasib

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

KRAS Targeted Compound Library

Publications Citing Use of MedChemExpress (MCE) Divarasib

Alle Ras Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Divarasib Related Classifications

HY-145928 Related Classifications