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Chemical Structure| 218457-67-1 Chemical Structure| 218457-67-1

Structure of CB-103
CAS No.: 218457-67-1

Chemical Structure| 218457-67-1

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CB-103 is a first-in-class orally active pan-notch signaling pathway inhibitor extracted from patent US9296682B2 with anti-tumor activity.

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Product Details of CB-103

CAS No. :218457-67-1
Formula : C15H18N2O
M.W : 242.32
SMILES Code : NC1=CC=C(OC2=CC=C(C(C)(C)C)C=C2)N=C1
MDL No. :MFCD00052647
InChI Key :WHIWGRCYMQLLAO-UHFFFAOYSA-N
Pubchem ID :2735289

Safety of CB-103

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Isoform Comparison

Biological Activity

Description
Limantrafin (CB-103) is a pioneering, orally bioavailable inhibitor of protein-protein interaction (PPI) targeting the NOTCH transcriptional activation complex. Limantrafin exhibits antitumor efficacy[1][2][3][4].

In Vitro:

Cell Line
Concentration Treated Time Description References
RPMI-8402 T-ALL cells 10 μM 72 hours CB-103 induces cell cycle arrest and apoptosis, impairing proliferation PMC7368267
HCC1187 TNBC cells 10 μM 6 days CB-103 inhibits growth of GSI-resistant tumor cells PMC7368267
HeLa cells 0.9 to 3.9 μM (IC50) 24 hours CB-103 inhibits Notch signaling, including Notch1, Notch2, Notch3, and Notch4-mediated signaling PMC7368267
HEK293 cells 0.5 and 2.5 µM 48 hours To evaluate the effect of CB-103 on the Notch signaling pathway, results showed a dose-dependent reduction in luciferase signal. PMC10444807
WHM20 1 µM and 5 µM 7 days To evaluate the effect of CB-103 alone or in combination with fulvestrant on mammosphere formation, results showed that CB-103 significantly inhibited mammosphere formation. PMC10416998
T47D/PKCα 1 µM and 5 µM 7 days To evaluate the effect of CB-103 alone or in combination with fulvestrant on mammosphere formation, results showed that CB-103 significantly inhibited mammosphere formation. PMC10416998
HCC1187 150 nM to 10 µM 72 hours To evaluate the synergistic effects of CB-103 with various anti-neoplastic drugs, results showed that CB-103 exhibited synergy with paclitaxel in HCC1187 cells. PMC10416998
MCF-7 150 nM to 10 µM 72 hours To evaluate the synergistic effects of CB-103 with various anti-neoplastic drugs, results showed that CB-103 exhibited synergy with fulvestrant and paclitaxel in MCF-7 cells. PMC10416998

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice PDX CTG-2308 (ER+ ESR1 wild type) Subcutaneous injection 40 mg/kg Once daily for 5 days To evaluate the effect of CB-103 in combination with fulvestrant on ER+ breast cancer models, results showed that combination therapy significantly delayed tumor growth. PMC10416998
Mice HCC1187 xenograft model Oral 25 mg/kg Twice daily for 15 days CB-103 significantly inhibits tumor growth and reduces tumor burden PMC7368267

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT03422679 Breast Cancer|Colorectal Cance... More >>r|Adenoid Cystic Carcinoma|Non-hodgkin Lymphoma|Glomus Tumor, Malignant|Hepatocellular Carcinoma|Osteosarcoma|T-ALL Less << PHASE1|PHASE2 TERMINATED 2022-11-11 Sarcoma Oncology Research Cent... More >>er, Santa Monica, California, 90403, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States|MD Anderson, Houston, Texas, 77030, United States|Centre Hospitalier Lyon-Sud, Lyon, France|H?pital Saint-Louis, Paris, 75475, France|Charite- Universitaetsmedizin Berlin- Campus Benjamin Franklin, Berlin, 10117, Germany|Universit?tsklinikum Frankfurt, Frankfurt, 60590, Germany|Nationales Centrum für Tumorerkrankungen Heidelberg, Heidelberg, 69120, Germany|Seoul National University Hospital, Seoul, 03080, Korea, Republic of|Severance Hospital - Yonsei Cancer Center, Seoul, 03722, Korea, Republic of|Seoul National University Hospital, Seoul, 06351, Korea, Republic of|Hospital Quirón Barcelona, Barcelona, 08023, Spain|Vall d'Hebron Institute of Oncology (VHIO), Barcelona, 08035, Spain|Catalan Institute of Oncology, Barcelona, 08916, Spain|Hospital Ramón y Cajal, Madrid, 28034, Spain|Oncology Institute of Southern Switzerland, Bellinzona, 6500, Switzerland|Kantonsspital St.Gallen, Saint Gallen, 9007, Switzerland Less <<
NCT04714619 Advanced Breast Cancer PHASE2 TERMINATED 2022-04-26 Complejo Hospitalario de Jaen,... More >> Jaen, Spain|Hospital Sant Joan de Reus, Reus, Spain Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.13mL

0.83mL

0.41mL

20.63mL

4.13mL

2.06mL

41.27mL

8.25mL

4.13mL

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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