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Chemical Structure| 602306-29-6 Chemical Structure| 602306-29-6

Structure of AZD-5438
CAS No.: 602306-29-6

Chemical Structure| 602306-29-6

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AZD5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16/6/20 nM.

Synonyms: AZD-5438

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Product Details of AZD-5438

CAS No. :602306-29-6
Formula : C18H21N5O2S
M.W : 371.46
SMILES Code : O=S(C1=CC=C(NC2=NC=CC(C3=CN=C(C)N3C(C)C)=N2)C=C1)(C)=O
Synonyms :
AZD-5438
MDL No. :MFCD11112135
InChI Key :WJRRGYBTGDJBFX-UHFFFAOYSA-N
Pubchem ID :16747683

Safety of AZD-5438

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of AZD-5438

Hedgehog

Isoform Comparison

Biological Activity

Target
  • CDK2

    CDK2, IC50:6 nM

  • CDK9

    CDK9, IC50:20 nM

  • CDK1

    CDK1, IC50:16 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
zebrafish larvae 50 nM 2 hours To test the synergistic protective effect of AZD-5438 with zorifertinib, results showed that AZD-5438 and zorifertinib at 50 nM concentration had a synergistic protective effect on excitotoxic damage in zebrafish larvae. PMC11186505
HEI-OC1 cells 0.700 μM 22 hours To evaluate the protective effect of AZD-5438 against cisplatin-induced cytotoxicity, the results showed an EC50 of 0.700 μM in HEI-OC1 cells. PMC6443376
mouse cochlear explants 0.34 nM 24 hours To test the protective effect of AZD5438 against cisplatin-induced hair cell death in cochlear explants, results showed that AZD5438 combined with dabrafenib provided enhanced protection compared to each drug alone. PMC7821884
P3 mouse cochlear explants 0.005 μM 24 hours To evaluate the protective effect of AZD-5438 against cisplatin-induced toxicity in cochlear explants, the results showed an EC50 of 0.005 μM in explants. PMC6443376
A549 75 nM 24 hours AZD5438 significantly enhanced the radiosensitivity of A549 cells, with a dose enhancement ratio (DER) of 1.5. PMC3623267
H1299 50 nM 24 hours AZD5438 significantly enhanced the radiosensitivity of H1299 cells, with a dose enhancement ratio (DER) of 1.3. PMC3623267
H460 200 nM 24 hours AZD5438 significantly enhanced the radiosensitivity of H460 cells, with a dose enhancement ratio (DER) of 1.3. PMC3623267
PANC-1 cells 0.5 μM, 0.1 μM, 0.02 μM 3 weeks AZD-5438 significantly inhibited the clonogenic capacity of PANC-1 cells, indicating its ability to suppress PDAC cell proliferation by activating C/EBPδ. PMC11783153
human naive pluripotent stem cells 0.1 µM 4-5 days AZD5438 was able to maintain the naive state of human naive pluripotent stem cells in feeder-free conditions and prevent exit from pluripotency. PMC6829768
Caco2 cells 5 μM 48 hours AZD5438 completely blocked the growth of Caco2 cells and induced apoptosis. PMC3945523
IEC-6 cells 1 μM 72 hours AZD5438 significantly reduced proliferation of IEC-6 cells and induced apoptosis. PMC3945523
HEK 293T cells 1 μM 72 hours AZD-5438, as a CDK inhibitor, significantly induced C/EBPδ-mediated eGFP fluorescence, indicating its ability to activate C/EBPδ transcriptional activity. PMC11783153

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice NOD/SCID mice Oral 20 mg/kg Once daily for three weeks To evaluate the antitumor activity of AZD-5438 in PDX models with high CCNE1 copy number. AZD-5438 showed significant antitumor activity in models with high CCNE1 copy number by inhibiting the expression of CDK2, CCNE1, and phosphorylated Rb. PMC5809945
BALB/c Nude mice AFPGC PDX models Oral 20 mg/kg Daily for 3 weeks To evaluate the antitumor efficacy of AZD5438 in CCNE1-amplified AFPGC PDX models, the results showed that AZD5438 significantly inhibited tumor growth in CCNE1-amplified models. PMC8225795
zebrafish excitotoxicity model in vitro culture 50 nM single dose, 2 hours To test the synergistic protective effect of AZD-5438 with zorifertinib, results showed that AZD-5438 and zorifertinib at 50 nM concentration had a synergistic protective effect on excitotoxic damage in zebrafish larvae. PMC11186505
Mice noise-induced hearing loss model Oral 35 mg/kg twice daily for 24, 48, and 72 hours To test the protective effect of AZD5438 against noise-induced hearing loss, results showed that AZD5438 combined with dabrafenib provided significant hearing protection. PMC7821884
FVB mice cisplatin-induced ototoxicity model transtympanic injection 50 μM 1 hour before cisplatin administration and again 24 hours after cisplatin administration To evaluate the protective effect of AZD-5438 against cisplatin-induced ototoxicity, the results showed that AZD-5438 significantly reduced ABR threshold shifts at 32 kHz, providing complete protection. PMC6443376
Nude mice Human xenograft model Oral 25 mg/kg/day Once daily for 5 days Combined treatment with AZD5438 and irradiation significantly enhanced tumor growth delay, with A549 and H1299 xenografts showing good response to the combined treatment. PMC3623267

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00088790 Neoplasms Phase 1 Completed - United States, Massachusetts ... More >> Research Site Boston, Massachusetts, United States United States, New York Research Site New York City, New York, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.46mL

2.69mL

1.35mL

26.92mL

5.38mL

2.69mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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