2. GPCR/G Protein MAPK/ERK Pathway PI3K/Akt/mTOR Apoptosis
  3. Ras p38 MAPK PI3K Apoptosis
  4. AZD4625

AZD4625 is an orally active, selective irreversible, covalent allosteric GTPase KRASG12C inhibitor with an IC50 of 3 nM. AZD4625 can inhibit the MAPK pathway (with decreased pCRAF, pMEK, and pERK) and the PI3K pathway (with decreased pAKT and pS6), and induce cell apoptosis. AZD4625 has no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. AZD4625 can be used for the study of KRASG12C mutant non-small cell lung cancer.

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

AZD4625

AZD4625 Chemical Structure

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Based on 1 publication(s) in Google Scholar

Other Forms of AZD4625:

AZD4625 Related Antibodies

Top Publications Citing Use of Products

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K-Ras H-Ras N-Ras Ras

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p38 MAPK p38α p38β MAPK13 p38δ p38γ

View All PI3K Isoform Specific Products:

View All Isoforms
PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

AZD4625 is an orally active, selective irreversible, covalent allosteric GTPase KRASG12C inhibitor with an IC50 of 3 nM. AZD4625 can inhibit the MAPK pathway (with decreased pCRAF, pMEK, and pERK) and the PI3K pathway (with decreased pAKT and pS6), and induce cell apoptosis. AZD4625 has no binding and inhibition of wild-type RAS or isoforms carrying non-KRASG12C mutations. AZD4625 can be used for the study of KRASG12C mutant non-small cell lung cancer[1][2].

IC50 & Target[1]

KRAS(G12C)

3 nM (IC50)

In Vitro

AZD4625 (Compound 21) inhibits p90RSK phosphorylation (IC50 = 36 nM) in KRASG12C mutant cells (NCI-H358)[1].
AZD4625 (0.01-3 μM, 0-120 h) reduces proliferation and survival of NCI-H358 cells (IC50 = 4.1 nM) driving cell-cycle arrest and apoptosis[1][2].
AZD4625 enhances the depth and duration of response when combined with the receptor tyrosine kinases (RTK) inhibitor SHP099 (HY-100388), the EGFR inhibitor Gefitinib (HY-50895) and ErbB inhibitor afatinib (HY-10261) in NCI-H358 and NCI-H1373 cells[2].

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

AZD4625 Related Antibodies

Apoptosis Analysis[2]

Cell Line: NCI-H358
Concentration: 0.01, 0.1, 1, 3 μM
Incubation Time: 0, 24, 48, 72, 96, 120 h
Result: Time- and concentration-dependently induced cell apoptosis.

Cell Cycle Analysis[2]

Cell Line: NCI-H358
Concentration: 0.1 and 1 μM
Incubation Time: 4 h
Result: Increased the proportion of G1 phase and decreased the proportion of S phase.
Parmacokinetics[1]
Species Dose Route Indicator value
Dog 1 mg/kg i.v. ClF_obs 17 mL/min/kg
Dog 2 mg/kg p.o. F 43 %
Mice 2 mg/kg i.v. ClF_obs 6 mL/min/kg
Mice 6 mg/kg p.o. F 77 %
Rat 1 mg/kg i.v. ClF_obs 22 mL/min/kg
Rat 2 mg/kg p.o. F 75 %
Dog 1 mg/kg i.v. Vss 1.4 L/kg
Mice 2 mg/kg i.v. Vss 0.6 L/kg
Rat 1 mg/kg i.v. Vss 0.7 L/kg
Dog 1 mg/kg i.v. T1/2 2.1 h
Mice 2 mg/kg i.v. T1/2 1.5 h
Rat 1 mg/kg i.v. T1/2 0.6 h
In Vivo

AZD4625 (Compound 21) (4-100 mg/kg, p.o., once daily for 15-20 days) inhibits tumor growth in KRASG12C MIAPaCa-2 xenograft mice model[1].
AZD4625 (4-100 mg/kg, p.o., once daily for 20-25 days) continuously inhibits tumor regression in the HCI-H358 xenograft mouse model, and appears relatively resistant in the HCI-H358 model, however, when combined with Afatinib and SHP099 shows a powerful anti-tumor effect NCI-H358 and LU99 lung xenograft models[2].
AZD4625 (100 mg/kg, p.o., once daily for 7 days) significantly reduces the lung tumor burden in six KRASG12C patient-derived xenograft (PDX) mice models[2].
AZD4625 (100 mg/kg , p.o., once daily for 21 days) drives changes to the tumor immune microenvironment and that deeper and more durable responses may be achieved if combined with immune checkpoint inhibitors (ICIs) in KRASG12C syngeneic mouse model[2].

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

Animal Model: KRASG12C MIAPaCa-2 xenograft model established in mice[1]
Dosage: 4, 20 and 100 mg/kg
Administration: Oral administration (p.o.), once daily for 15-20 days
Result: Significantly inhibited the growth of MIA PaCa-2 tumors at 100 mg/kg.
Showed a robust, dose-dependent decrease in the expression of DUSP6.
Animal Model: NCI-H358, NCI-H2122, and LU99 xenograft model established in mice[2]
Dosage: 4, 20 and 100 mg/kg
Administration: Oral administration (p.o.), once daily for 20-25 days
Result: significantly inhibited the growth of NCI-H358 and NCI-H2122 models at 100 mg/kg.
Was well tolerated with no effects on animal body weight on chronic daily dosing.
Enhanced the anti-tumor effect with Afatinib and SHP099 in NCI-H2122, and LU99 xenograft model.
Animal Model: PDX model established in female athymic nude-Foxn1nu mice or female BALB/cNj nude mice[2]
Dosage: 100 mg/kg
Administration: Oral administration (p.o.), once daily for 7 days
Result: Observed tumor growth inhibition and regression, with the lung tumor models appearing broadly more sensitive than colorectal.
Animal Model: CT26G12C syngeneic model established in female BALB/cOla mice[2]
Dosage: 100 mg/kg
Administration: Oral administration (p.o.), once daily for 21 days
Result: Induced an initial regression, but 100% of the tumors recured.
Significantly prolonged survival period, with no recurrence after discontinuation of treatment combined with anti-PD-1 or anti-PD-L1.
Molecular Weight

486.90

Formula

C24H21ClF2N4O3
Appearance

Solid

Color

White to off-white

SMILES

C=CC(N1C[C@H]2N(C3=C4C(OCC2)=C(Cl)[C@@]([C@@]5=C(F)C=CC=C5O)=C(F)C4=NC=N3)C[C@H]1C)=O
Shipping

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

DMSO : 100 mg/mL (205.38 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 2.0538 mL 10.2690 mL 20.5381 mL
5 mM 0.4108 mL 2.0538 mL 4.1076 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)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

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: ≥ 2.08 mg/mL (4.27 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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: ≥ 2.08 mg/mL (4.27 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 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:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
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: 99.52%

SDS (251 KB)

COA (259 KB) HNMR (425 KB) LCMS (96 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 2.0538 mL 10.2690 mL 20.5381 mL 51.3452 mL
5 mM 0.4108 mL 2.0538 mL 4.1076 mL 10.2690 mL
10 mM 0.2054 mL 1.0269 mL 2.0538 mL 5.1345 mL
15 mM 0.1369 mL 0.6846 mL 1.3692 mL 3.4230 mL
20 mM 0.1027 mL 0.5135 mL 1.0269 mL 2.5673 mL
25 mM 0.0822 mL 0.4108 mL 0.8215 mL 2.0538 mL
30 mM 0.0685 mL 0.3423 mL 0.6846 mL 1.7115 mL
40 mM 0.0513 mL 0.2567 mL 0.5135 mL 1.2836 mL
50 mM 0.0411 mL 0.2054 mL 0.4108 mL 1.0269 mL
60 mM 0.0342 mL 0.1712 mL 0.3423 mL 0.8558 mL
80 mM 0.0257 mL 0.1284 mL 0.2567 mL 0.6418 mL
100 mM 0.0205 mL 0.1027 mL 0.2054 mL 0.5135 mL
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AZD4625 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:

AZD4625AZD 4625AZD-4625Rasp38 MAPKPI3KApoptosisPhosphoinositide 3-kinaseNon-small cell lung cancerKRASG12CNCI-H358 cellsXenograft mice modelOral bioavailabilityInhibitorinhibitorinhibit

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