2. PROTAC Protein Tyrosine Kinase/RTK
  3. PROTACs Anaplastic lymphoma kinase (ALK)
  4. PROTAC ALK5 Degrader-1

PROTAC ALK5 Degrader-1 is a selective ALK5 PROTAC degrader. PROTAC ALK5 Degrader-1 induces ALK5 degradation via ALK5 ATP-binding pocket engagement, CRBN recruitment, and the ubiquitin-proteasome system.PROTAC ALK5 Degrader-1 inhibits ALK5 downstream signaling. PROTAC ALK5 Degrader-1 can be used for the research of pulmonary fibrosis.
(Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-183441); Blue: Cereblon ligand (HY-14658); Black: linker (HY-183440)).

For research use only. We do not sell to patients.

PROTAC ALK5 Degrader-1

PROTAC ALK5 Degrader-1 Chemical Structure

CAS No. : 3125240-35-6

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PROTAC ALK5 Degrader-1 Related Antibodies

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Description

PROTAC ALK5 Degrader-1 is a selective ALK5 PROTAC degrader. PROTAC ALK5 Degrader-1 induces ALK5 degradation via ALK5 ATP-binding pocket engagement, CRBN recruitment, and the ubiquitin-proteasome system.PROTAC ALK5 Degrader-1 inhibits ALK5 downstream signaling. PROTAC ALK5 Degrader-1 can be used for the research of pulmonary fibrosis[1]. (Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-183441); Blue: Cereblon ligand (HY-14658); Black: linker (HY-183440)).

In Vitro

PROTAC ALK5 Degrader-1 (Compound A31) (0.1-1 μM; 24 h) induces ALK5 degradation in NIH3T3 cells[1].
PROTAC ALK5 Degrader-1 (1 μM; 2-48 h) induces time-dependent ALK5 degradation in NIH3T3 cells[1].
PROTAC ALK5 Degrader-1 (0.37-30 μM; 24 h) induces concentration-dependent ALK5 degradation in NIH3T3 cells over 24 h[1].
PROTAC ALK5 Degrader-1 (1 μM; 48 h) selectively induces ALK5 degradation over the related ALK4 receptor in NIH3T3 cells[1].
PROTAC ALK5 Degrader-1 (1 μM; 48 h)-induced ALK5 degradation in NIH3T3 cells is reversible, with gradual recovery of ALK5 protein levels following compound wash-out after 48 h of 1 μM treatment[1].
PROTAC ALK5 Degrader-1 (1 μM; 48 h)-induced ALK5 degradation in NIH3T3 cells requires engagement of the ALK5 ATP-binding pocket, CRBN recruitment, and the ubiquitin-proteasome system[1].
PROTAC ALK5 Degrader-1 (1 μM; 48 h) suppresses phosphorylation of ALK5 downstream effectors Smad2/3, AKT, and ERK1/2 in TGF-β1-stimulated NIH3T3 cells[1].
PROTAC ALK5 Degrader-1 (0.2-5 μM; 48 h) dose-dependently inhibits TGF-β1-induced upregulation of fibrotic markers Collagen I and α-SMA in NIH3T3 cells[1].
PROTAC ALK5 Degrader-1 (0.2-5 μM; 48 h) dose-dependently reduces the fluorescence intensity of fibrotic markers Collagen I and α-SMA in TGF-β1-stimulated NIH3T3 cells following 1 h of TGF-β1 stimulation[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

PROTAC ALK5 Degrader-1 Related Antibodies

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 0.1 μM; 1 μM
Incubation Time: 24 h
Result: Induced 18% ALK5 degradation at 0.1 μM.
Induced 49% ALK5 degradation at 1 μM.

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 1 μM
Incubation Time: 2 h; 4 h; 8 h; 12 h; 24 h; 48 h
Result: Detected reduction in ALK5 levels starting at 24 h.
Showed progressive degradation over time, reaching maximal effect at 48 h.

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 0.37 μM; 1.1 μM; 3.3 μM; 10 μM; 30 μM
Incubation Time: 24 h
Result: Elicited ALK5 degradation at 0.37 μM.
Showed most pronounced degradation effect at 1.1 μM.
Exhibited reduced degradation efficiency at concentrations above 1.1 μM, consistent with a hook effect-like phenomenon.
Did not achieve 50% degradation within the tested concentration range.

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 1 μM
Incubation Time: 48 h
Result: Efficiently degraded ALK5.
Barely degraded ALK4 under the same experimental conditions.
Kept ALK5 protein levels suppressed under continuous treatment.
Showed gradual recovery of ALK5 protein levels after compound wash-out.

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 1 μM
Incubation Time: 48 h
Result: Significantly reduced phosphorylation of Smad2/3, AKT, and ERK1/2.
Did not alter total protein levels of Smad2/3, AKT, and ERK1/2.

Western Blot Analysis[1]

Cell Line: NIH3T3
Concentration: 0.2 μM; 1 μM; 5 μM
Incubation Time: 48 h
Result: Dose-dependently attenuated the TGF-β1-induced increase in Collagen I protein expression.
Dose-dependently attenuated the TGF-β1-induced increase in α-SMA protein expression.

Immunofluorescence[1]

Cell Line: NIH3T3
Concentration: 0.2 μM; 1 μM; 5 μM
Incubation Time: 48 h
Result: Dose-dependently reduced the fluorescence intensity of Collagen I.
Dose-dependently reduced the fluorescence intensity of α-SMA.
Confirmed attenuation of TGF-β1-induced fibroblast activation.
Parmacokinetics
Species Dose Route AUC0-t AUC0-∞ MRT0-t MRT0-∞ T1/2 Tmax Cmax F
Mice[1] 1 mg/kg i.v. 264.94 μg/L·h 263.61 μg/L·h 0.48 h 0.50 h 1.33 h 0.08 h 678.84 μg/L /
Mice[1] 10 mg/kg p.o. 7.36 μg/L·h 7.50 μg/L·h 0.36 h 0.48 h 0.50 h 0.08 h 28.67 μg/L 0.28 %
Mice[1] 10 mg/kg i.p. 1869.79 μg/L·h 1875.37 μg/L·h 1.67 h 1.75 h 4.24 h 0.33 h 1139.89 μg/L 70.57 %
In Vivo

PROTAC ALK5 Degrader-1 (Compound A31) (15-30 mg/kg; i.p.; daily; 14 days) dose-dependently exhibits potent in vivo anti-fibrotic efficacy in a Bleomycin (HY-108345)-induced mouse pulmonary fibrosis model, with greater activity than dose-matched TP008 (HY-125851) across multiple endpoints, and shows no significant systemic toxicity at efficacious doses[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 (Bleomycin-induced pulmonary fibrosis model)[1]
Dosage: 15 mg/kg; 30 mg/kg
Administration: i.p.; daily; 14 days
Result: Alleviated Bleomycin-induced body weight loss compared to vehicle-treated mice.
Reduced lung index by 10.6% at 15 mg/kg relative to dose-matched TP008.
Reduced fibrosis score by 9.8% at 15 mg/kg relative to dose-matched TP008, with efficacy comparable to nintedanib.
Reduced collagen positive percentage by 15.9% at 15 mg/kg relative to dose-matched TP008, restoring collagen levels toward sham control at both doses.
Reduced Collagen I fluorescence intensity by 15% and α-SMA fluorescence intensity by 20% at 15 mg/kg relative to dose-matched TP008, with efficacy comparable to nintedanib at both doses.
Reduced the proportion of lung dendritic cells (CD11c+ MHCII+) with greater efficacy than nintedanib, and attenuated bleomycin-induced accumulation of F4/80+ CD11b+ CD206+ macrophages with effects comparable to nintedanib, in a dose-dependent manner.
Reduced lung tissue ALK5 protein levels and suppressed downstream signaling activation (p-Smad2/3, p-AKT, p-ERK1/2) in a dose-dependent manner; showed greater suppression of p-AKT (additional 27%) and p-ERK1/2 (additional 79%) at 15 mg/kg relative to dose-matched TP008.
Showed no significant systemic toxicity: histopathology of heart, liver, spleen, and kidneys showed normal tissue architecture, and serum ALT/AST levels were not significantly different from sham controls.
Molecular Weight

852.31

Formula

C43H43ClFN9O7
CAS No.
SMILES

ClC1=CC(C2=CC(N3C4=CC=NC=C4N(CC(NCCN5CCN(CCCCOC6=CC=CC(C(N7C8C(NC(CC8)=O)=O)=O)=C6C7=O)CC5)=O)C3=O)=C(C)C=N2)=C(F)C=C1
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Purity & Documentation
References
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PROTAC ALK5 Degrader-1 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PROTAC ALK5 Degrader-13125240-35-6PROTACsAnaplastic lymphoma kinase (ALK)Anaplastic lymphoma kinaseALK tyrosine kinase receptorCD246Cluster of differentiation 246ALK4 receptorSmad2/3pulmonary fibrosisTGF-β1ERK1/2CRBNubiquitin-proteasome systemAKTALK5NIH3T3 cellsInhibitorinhibitorinhibit

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