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Chemical Structure| 1235034-55-5 Chemical Structure| 1235034-55-5

Structure of A-1155463
CAS No.: 1235034-55-5

Chemical Structure| 1235034-55-5

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A-1155463 is a highly selective BCL-XL inhibitor with an EC50 of 70 nM in Molt-4 cells.

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Product Details of A-1155463

CAS No. :1235034-55-5
Formula : C35H32FN5O4S2
M.W : 669.79
SMILES Code : O=C(C1=C(CCCOC2=CC=C(C#CCN(C)C)C=C2F)SC(N3CC4=C(C=CC=C4C(NC5=NC6=CC=CC=C6S5)=O)CC3)=N1)O
MDL No. :MFCD29924714
InChI Key :SOYCFODXNRVBTI-UHFFFAOYSA-N
Pubchem ID :59447577

Safety of A-1155463

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
GEO 200 nM 72 hours Evaluate the effect of BCL-XL siRNA on cell viability, results showed minimal change in survival of resistant cell lines. Mol Cancer. 2015 Jul 2;14:126.
RKO 200 nM 72 hours Evaluate the effect of BCL-XL siRNA on cell viability, results showed minimal change in survival of resistant cell lines. Mol Cancer. 2015 Jul 2;14:126.
SW1417 200 nM 72 hours Evaluate the effect of BCL-XL siRNA on cell viability, results showed significant reduction in survival of sensitive cell lines. Mol Cancer. 2015 Jul 2;14:126.
LS1034 200 nM 72 hours Evaluate the effect of BCL-XL siRNA on cell viability, results showed significant reduction in survival of sensitive cell lines. Mol Cancer. 2015 Jul 2;14:126.
SU-DHL-8 and RCK8 cell lines 446.4 nM and 167.4 nM Evaluate the sensitivity of BCL2Low NHL cell lines to A-1155463, showing that SU-DHL-8 and RCK8 were sensitive to A-1155463. Blood Cancer J. 2015 Nov 13;5(11):e368.
HEK293T cells 100 nM 24 hours abolished Bcl-XL-mediated enhancement of surface α7 nAChR expression Nat Commun. 2019 Jun 21;10(1):2746.
Z-138 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 4.96E-08, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
REC-1 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 0.185, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
JEKO-1 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 1.15E-03, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
MINO 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 8.62E-04, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
UPF1H 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 0.003, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
MAVER-1 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 0.009, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
HBL-2 1000 nM 24 hours Evaluated the synergy between VEN and A1155463, showing a combination index (CI) of 0.150, indicating strong synergy. Blood Adv. 2024 Jul 9;8(13):3532-3543.
LP-9 62.5, 125, 250 nM 48 hours No significant apoptosis increase Cell Death Dis. 2021 Apr 15;12(4):406.
MESO-1 62.5, 125, 250 nM 48 hours Induced apoptosis, 4-5.4-fold increase in Annexin V-positive cells Cell Death Dis. 2021 Apr 15;12(4):406.
Normal mesothelial cells (LP-9) 62.5, 125, 250 nM 48 hours To evaluate the effect of A-1155463 on normal mesothelial cells. Results showed A-1155463 had minimal effect on apoptosis in LP-9 cells. Cell Death Dis. 2021 Apr 15;12(4):406.
MPM cells (MESO-1, MESO-4, JL-1, H2452, MSTO-211H, H28, H2052) 62.5, 125, 250 nM 48 hours To evaluate the effect of A-1155463 on MPM cell proliferation and apoptosis. Results showed A-1155463 significantly inhibited MPM cell proliferation and induced apoptosis. Cell Death Dis. 2021 Apr 15;12(4):406.
NHL cell lines 0-20μM 48 hours Evaluate the effect of BCL-XL selective inhibitor A-1155463 on the survival of NHL cell lines, showing that BCL2High cell lines were resistant to A-1155463 (EC50 45μM). Blood Cancer J. 2015 Nov 13;5(11):e368.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice Patient-derived xenograft (PDX) models VEN (oral gavage), A1155463 (intraperitoneally) 10 mg/kg 4 days on/3 days off, for 2 weeks Evaluated the antitumor efficacy of the combination of VEN and A1155463, showing significant tumor growth inhibition even in VEN-resistant models. Blood Adv. 2024 Jul 9;8(13):3532-3543.
NSG mice MESO-1 xenograft model Intraperitoneal injection 5 mg/kg Once daily for 23 days To evaluate the efficacy of A-1155463 combined with HCQ in MPM xenografts. Results showed the combination treatment significantly suppressed tumor growth and induced apoptosis. Cell Death Dis. 2021 Apr 15;12(4):406.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.49mL

0.30mL

0.15mL

7.47mL

1.49mL

0.75mL

14.93mL

2.99mL

1.49mL

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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