SJ11646
Based on 1 Customer Validation
SJ11646 is a LCK PROTAC degrader with a DC50 value of 0.00838 pM against LCK. SJ11646 recruits CRBN and LCK to form a ternary complex, inducing cereblon-mediated proteasomal degradation of LCK. SJ11646 induces cytotoxicity in T-ALL cells, but such cytotoxicity is reduced in cells harboring the LCKT316I mutation. SJ11646 can be used in studies related to T-cell acute lymphoblastic leukemia.
(Pink: Lck ligand (HY-107447); Blue: Cereblon ligand (HY-163169); Black: linker (HY-76667)).
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- Pureté: 99.3%
- CAS No.: 2933135-82-9
- Formule: C36H40ClN9O5S
- Masse moléculaire:746.28
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Stockage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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Lck 0.00838 pM (DC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| KOPTK1 | LC50 |
0.083 pM
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Cytotoxicity (growth inhibition) against human KOPT-K1 T-ALL cells assessed via CellTiter-Glo (CTG) assay.
Cytotoxicity (growth inhibition) against human KOPT-K1 T-ALL cells assessed via CellTiter-Glo (CTG) assay.
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40672235 |
| CD34+ cells | LC50 |
726.42 nM
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Cytotoxicity against normal human cord blood CD34+ cells assessed via CellTiter-Glo (CTG) assay after 3 days incubation.
Cytotoxicity against normal human cord blood CD34+ cells assessed via CellTiter-Glo (CTG) assay after 3 days incubation.
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40672235 |
| PBMC | LC50 |
13.84 nM
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Cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs) assessed via CellTiter-Glo (CTG) assay after 3 days incubation.
Cytotoxicity against normal human peripheral blood mononuclear cells (PBMCs) assessed via CellTiter-Glo (CTG) assay after 3 days incubation.
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40672235 |
| SUP-B15 | LC50 |
0.0123 pM
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Cytotoxicity against human SUP-B15 B-ALL cells (BCR-ABL fusion-positive) assessed via CellTiter-Glo (CTG) assay.
Cytotoxicity against human SUP-B15 B-ALL cells (BCR-ABL fusion-positive) assessed via CellTiter-Glo (CTG) assay.
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40672235 |
SJ11646 (10-7-100 nM; 1-24 h) induces CRBN-dependent LCK degradation and cytotoxicity in KOPT-K1 T-ALL cells with a DC50 of 0.00838 pM, and sustains growth inhibition and suppression of the LCK signaling pathway even after removal[1].
SJ11646 (10-2-104 nM; 96 h) exhibits selective cytotoxicity against LCK-dependent T-ALL blasts in xenografts, while showing no effect on LCK-independent T-ALL cells[1].
SJ11646 (100 nM; 24 h) selectively degrades SRC family kinases (including LCK) in KOPT-K1 T-ALL cells[1].
SJ11646 induces cereblon-dependent LCK degradation and cytotoxicity in KOPT-K1 T-ALL cells[1].
SJ11646 (10-3-10 μM; 72 h) exhibits cytotoxic activity against wild-type KOPT-K1 T-ALL cells[2].
SJ11646 (10-3-10 μM; 72 h) exhibits significantly reduced cytotoxic activity against Dasatinib (HY-10181)-resistant KOPT-K1 T-ALL cells harboring the LCKT316I mutation[2].
SJ11646 (10 nM; 24 h) induces significant LCK degradation in wild-type KOPT-K1 T-ALL cells, but this degradation effect is greatly attenuated in LCKT316I mutation-harboring drug-resistant KOPT-K1 cells at concentrations ranging from 10-3 to 10 μM[1].
SJ11646 (10-3-10 μM; 24 h) potently induces dose-dependent degradation of LCK in KOPT-K1 T-ALL cells[2].
SJ11646 (10-5-105 nM; 72 h) degrades BCR-ABL and induces potent cytotoxicity in SUP-B15 B-ALL cells, with an LC50 of 0.0123 pM[2].
SJ11646 (10-4-10 μM; 1 h) potently induces the formation of a ternary complex between LCKG415N and CRBN-DDB1[2].
SJ11646 (10-4-10 μM; 1 h) induces the formation of a ternary complex between wild-type LCK and CRBN-DDB1[2].
SJ11646 (10-2-104 nM; 72 h) exhibits lower cytotoxicity than Dasatinib against normal human umbilical cord blood CD34+ cells and peripheral blood mononuclear cells, and exerts comparable effects on resting and activated normal T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:KOPT-K1 T-ALL cells
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Concentration:10-7, 10-6, 10-5, 10-4, 10-3, 10-2, 10-1, 1, 10, 100 nM
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Incubation Time:24 h
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Result:Suppressed KOPT-K1 cell growth for up to 24 hours post-removal, with pLCK remaining undetectable for the same period.
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Cell Line:KOPT-K1 T-ALL cells, SUP-B15 B-ALL cells (BCR-ABL fusion-positive)
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Concentration:100 nM
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Incubation Time:6 h
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Result:Identified only CSK, LCK, and SRC as proteins uniquely affected by treatment, with DUSP6 and CISH (LCK downstream signaling proteins).
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Cell Line:Wildtype KOPT-K1 T-cell acute lymphoblastic leukemia (T-ALL) cells
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Concentration:10-3, 10-2, 10-1, 1, 10 μM
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Incubation Time:72 h
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Result:Exhibited cytotoxic activity against wildtype KOPT-K1 cells.
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Cell Line:Wildtype and dasatinib-resistant (LCK T316I) KOPT-K1 T-ALL cells
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Concentration:10 nM
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Incubation Time:24 h
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Result:Induced substantial LCK degradation in wildtype KOPT-K1 cells, but LCK degradation was greatly compromised in Dasatinib-resistant KOPT-K1 cells harboring the LCK T316I mutation.
| Species | Dose | Route | T1/2 | AUC0-∞ |
|---|---|---|---|---|
| Mice[2] | 15 mg/kg | i.p. | 1.3 h | 1382 ng/mL·h |
SJ11646 (15 mg/kg; i.p.; single administration) extends the duration of > 50% LCK phosphorylation inhibition by 630% (up to 52 h) in T-ALL PDX mice, with a maximum pLCK depletion rate of 97%[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) (female, 8-12 weeks of age, tail vein injection of 2 million primary human T-ALL cells)[2]
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Dosage:15 mg/kg
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Administration:i.p.; once daily for 8 weeks
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Result:Reduced blood blast percentage to 12.9% and 0.9% in PDX_1 and PDX_2, respectively.
Markedly increased leukemia-free survival.
Caused no significant bodyweight changes or gross toxicities during treatment.
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Animal Model:NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) (female, 8-12 weeks of age, tail vein injection of primary human T-ALL cells)[2]
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Dosage:15 mg/kg
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Administration:i.p.; single dose
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Result:Induced rapid and complete loss of pLCK within 3 hours post-injection, with prolonged suppression of pLCK lasting at least 24 hours and concomitant LCK degradation.
Chemical Information
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CAS No. 2933135-82-9
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Appearance Solid
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Masse moléculaire 746.28
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Formule C36H40ClN9O5S
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Color White to off-white
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SMILES
O=C(C1=CN=C(NC2=NC(C)=NC(N3CCN(CCCNC(COC4=CC=C(C(CC5)C(NC5=O)=O)C=C4)=O)CC3)=C2)S1)NC6=C(C)C=CC=C6Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Pureté et documentation
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Fiche technique (275 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
[1]. Yang JJ, et al. LCK-targeting molecular glues overcome resistance to inhibitor-based therapy in T-cell acute lymphoblastic leukemia. bioRxiv [Preprint]. 2025 Jul 7:2025.07.03.663042. [Content Brief]
[2]. Hu J, et al. Preclinical evaluation of proteolytic targeting of LCK as a therapeutic approach in T cell acute lymphoblastic leukemia. Science translational medicine. 2022 Aug 24;14(659):eabo5228. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SJ11646 Related Classifications
HY-175281 Related Classifications
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