- Advanced equipment and technique
- Experienced scientific team
- Highly reliable and reproducible result
- Data analysis, detailed report with results and discussion
- Quality one-stop service

PROTAC Bcl-xL degrader-3 - CAS 2471970-60-0

Inquiry

It is a potent BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity.

* Please be kindly noted that our services and products can only be used for research to organizations or companies and not intended for any clinical or individuals.

Molecular Formula

C82H105ClF3N11O11S4

Molecular Weight

1641.49

PROTAC Bcl-xL degrader-3

- Specification
  - IUPAC Name
    
    (2S,4R)-1-[(2S)-2-[[8-[4-[[(1R)-4-(4-chlorophenyl)-1-methyl-3-[[4-[4-[[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylcarbamoyl]phenyl]piperazin-1-yl]methyl]cyclohex-3-en-1-yl]methyl]piperazin-1-yl]-8-oxooctanoyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
    
    Synonyms
    
    753b; (2S,4R)-1-((S)-2-(8-(4-(((R)-4'-chloro-4-methyl-6-((4-(4-(((4-(((R)-4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)carbamoyl)phenyl)piperazin-1-yl)methyl)-2,3,4,5-tetrahydro-[1,1'-biphenyl]-4-yl)methyl)piperazin-1-yl)-8-oxooctanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide
- Properties
  - Density
    
    1.39±0.1 g/cm3
    
    InChI Key
    
    KQEMZZJSHJCPSI-RYFXIQSLSA-N
    
    InChI
    
    InChI=1S/C82H105ClF3N11O11S4/c1-56(58-18-20-60(21-19-58)75-57(2)87-55-110-75)88-78(102)71-48-66(98)52-97(71)79(103)76(80(3,4)5)90-73(99)16-12-7-8-13-17-74(100)96-42-38-94(39-43-96)54-81(6)34-32-69(59-22-26-63(83)27-23-59)62(50-81)51-93-36-40-95(41-37-93)65-28-24-61(25-29-65)77(101)91-112(106,107)68-30-31-70(72(49-68)111(104,105)82(84,85)86)89-64(33-35-92-44-46-108-47-45-92)53-109-67-14-10-9-11-15-67/h9-11,14-15,18-31,49,55-56,64,66,71,76,89,98H,7-8,12-13,16-17,32-48,50-54H2,1-6H3,(H,88,102)(H,90,99)(H,91,101)/t56-,64+,66+,71-,76+,81+/m0/s1
    
    Canonical SMILES
    
    CC1=C(SC=N1)C2=CC=C(C=C2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCCCCCC(=O)N4CCN(CC4)CC5(CCC(=C(C5)CN6CCN(CC6)C7=CC=C(C=C7)C(=O)NS(=O)(=O)C8=CC(=C(C=C8)NC(CCN9CCOCC9)CSC1=CC=CC=C1)S(=O)(=O)C(F)(F)F)C1=CC=C(C=C1)Cl)C)O
- Reference Reading
  - 1. Development of a BCL-xL and BCL-2 dual degrader with improved anti-leukemic activity.
    
    Lv, D., Pal, P., Liu, X., Jia, Y., Thummuri, D., Zhang, P., Hu, W., Pei, J., Zhang, Q., Zhou, S. and Khan, S., 2021. Nature communications, 12(1), pp.1-14.
    
    PROteolysis-TArgeting Chimeras (PROTACs) have emerged as an innovative drug development platform. However, most PROTACs have been generated empirically because many determinants of PROTAC specificity and activity remain elusive. Through computational modelling of the entire NEDD8-VHL Cullin RING E3 ubiquitin ligase (CRLVHL)/PROTAC/BCL-xL/UbcH5B(E2)-Ub/RBX1 complex, we find that this complex can only ubiquitinate the lysines in a defined band region on BCL-xL. Using this approach to guide our development of a series of ABT263-derived and VHL-recruiting PROTACs, we generate a potent BCL-xL and BCL-2 (BCL-xL/2) dual degrader with significantly improved antitumor activity against BCL-xL/2-dependent leukemia cells. Our results provide experimental evidence that the accessibility of lysines on a target protein plays an important role in determining the selectivity and potency of a PROTAC in inducing protein degradation, which may serve as a conceptual framework to guide the future development of PROTACs.

Bio Calculators

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂

Calculate

* Total Molecular Weight:

g/mol

Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳

Formula weight: *

g/mol

Desired final volume: *

Desired concentration: *