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Chemical Structure| 1313363-54-0 Chemical Structure| 1313363-54-0

Structure of NVP-CGM097
CAS No.: 1313363-54-0

Chemical Structure| 1313363-54-0

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NVP-CGM097 is a potent, selective and species specific p53-Mdm2 inhibitor with IC50 of 1.7±0.1 nM.

Synonyms: CGM097

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Product Details of NVP-CGM097

CAS No. :1313363-54-0
Formula : C38H47ClN4O4
M.W : 659.26
SMILES Code : O=C1N(C2=CC=C(N(C)C[C@H]3CC[C@H](N4CC(N(C)CC4)=O)CC3)C=C2)[C@@H](C5=CC=C(Cl)C=C5)C6=C(C=C(OC)C(OC(C)C)=C6)C1
Synonyms :
CGM097
MDL No. :MFCD28144684
InChI Key :CLRSLRWKONPSRQ-CPOWQTMSSA-N
Pubchem ID :53240420

Safety of NVP-CGM097

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

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
SJSA-1 352 ±190 nM Evaluate the anti-proliferative effects of NVP-CGM097 PMC4468608
HCT116 p53WT 454 ±136 nM Evaluate the anti-proliferative effects of NVP-CGM097 PMC4468608
MCF-7 PalbR 1 μM 48 hours To evaluate the anti-tumor effects of NVP-CGM097 on palbociclib-resistant MCF-7 cells, showing cell cycle arrest and increased senescence. PMC7425060
MCF-7 FasR 1 μM 48 hours To evaluate the anti-tumor effects of NVP-CGM097 on fulvestrant-resistant MCF-7 cells, showing cell cycle arrest and increased senescence. PMC7425060
T-47D 1 μM 48 hours To evaluate the anti-tumor effects of NVP-CGM097 on p53 mutant ER-positive breast cancer cells, showing no significant effect. PMC7425060
ZR75-1 1 μM 48 hours To evaluate the anti-tumor effects of NVP-CGM097 on p53 wild-type ER-positive breast cancer cells, showing cell cycle arrest and increased apoptosis. PMC7425060
MCF-7 1 μM 48 hours To evaluate the anti-tumor effects of NVP-CGM097 on p53 wild-type ER-positive breast cancer cells, showing cell cycle arrest and increased apoptosis. PMC7425060
B-ALL PDX cells 2 μM 18 hours To assess the accuracy of dynamic BH3 profiling as a predictor of in vivo response to CGM097, results showed that Δ% priming with PUMA BH3 peptide perfectly discriminated B-ALL PDXs responsive to CGM097 treatment. PMC5177991
RPE.1 cells 10μM 16 hours Assess the effect of MYCN expression on the combination of NVP-CGM097 and venetoclax, showing increased apoptosis with MYCN expression PMC10350345
MYCN-amplified neuroblastoma cell lines 1μM 16 hours Evaluate the synergy of NVP-CGM097 with venetoclax, showing synergistic killing in MYCN-amplified neuroblastoma cells PMC10350345

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD-SCID-IL2γR−/− mice KCC_P_3837 PDX model Oral gavage 100 mg/kg 5 days a week for 60 days To evaluate the anti-tumor effects of NVP-CGM097 on endocrine-sensitive ER-positive breast cancer PDX model, showing significant tumor growth inhibition. PMC7425060
NSG mice B-ALL PDX model Oral gavage 100 mg/kg Once daily until mice met criteria for sacrifice To evaluate the efficacy of CGM097 in B-ALL PDX models, results showed that CGM097 significantly prolonged survival in mice engrafted with wild-type TP53 B-ALL PDXs. PMC5177991
NSG mice AML patient-derived mouse xenograft model Oral 100 mg/kg Once daily for 34 days CGM097 significantly reduced in vivo tumor growth and was well-tolerated PMC4596780
NSG mice COG-N-561x and COG-N-415x PDX models Oral gavage 50mg/kg 5 days/week for two weeks Evaluate the in vivo synergy of NVP-CGM097 with venetoclax, showing significant tumor shrinkage with combination therapy PMC10350345
Mice SJSA-1 osteosarcoma xenograft model Oral 100 mg/kg Daily for 4 weeks Evaluate the anti-tumor activity of NVP-CGM097 in vivo PMC4468608

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT01760525 Solid Tumor With p53 Wild Type... More >> Status Less << PHASE1 COMPLETED 2020-07-24 Dana Farber Cancer Institute S... More >>C (2), Boston, Massachusetts, 02215, United States|Novartis Investigative Site, Lyon Cedex, 69373, France|Novartis Investigative Site, Essen, 45147, Germany|Novartis Investigative Site, Singapore, 169610, Singapore|Novartis Investigative Site, Zuerich, 8091, Switzerland Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.52mL

0.30mL

0.15mL

7.58mL

1.52mL

0.76mL

15.17mL

3.03mL

1.52mL

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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