2. PROTAC Epigenetics
  3. PROTACs Epigenetic Reader Domain
  4. CW-3308

CW-3308 is an orally active BRD9 PROTAC degrader with an DC50 of 92 nM. CW-3308 forms a ternary complex with BRD9 and cereblon to mediate BRD9 degradation. CW-3308 inhibits the viability of synovial sarcoma and rhabdoid tumor cells. CW-3308 reduces BRD9 protein levels in xenograft tumor tissues and suppresses tumor growth in xenograft models. CW-3308 can be used for the research of synovial sarcoma and rhabdoid tumors.
(Pink: BRD9 ligand (HY-159596); Blue: Cereblon ligand (HY-159597); Black: linker (HY-159598)).

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

CW-3308

CW-3308 Chemical Structure

CAS No. : 3055592-99-6

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Based on 1 publication(s) in Google Scholar

CW-3308 Related Antibodies

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Description

CW-3308 is an orally active BRD9 PROTAC degrader with an DC50 of 92 nM. CW-3308 forms a ternary complex with BRD9 and cereblon to mediate BRD9 degradation. CW-3308 inhibits the viability of synovial sarcoma and rhabdoid tumor cells. CW-3308 reduces BRD9 protein levels in xenograft tumor tissues and suppresses tumor growth in xenograft models. CW-3308 can be used for the research of synovial sarcoma and rhabdoid tumors[1]. (Pink: BRD9 ligand (HY-159596); Blue: Cereblon ligand (HY-159597); Black: linker (HY-159598)).

IC50 & Target[1]

BRD9

5 nM (IC50)

Cereblon

 

Cellular Effect
Cell Line Type Value Description References
G-401 IC50
185 nM
Compound: 27; CW-3308
Inhibition of cell viability in human G-401 cells incubated for 4 days by CellTiter-Glo luminescent cell viability assay
Inhibition of cell viability in human G-401 cells incubated for 4 days by CellTiter-Glo luminescent cell viability assay
[PMID: 39132814]
In Vitro

CW-3308 (Compound 27) potently degrades BRD9 in genetically engineered HEK293 CRISPR knock-in cells after 6 h, with a DC50 of 92 nM and a maximum degradation rate of 99%[1].
CW-3308 (0.1-1000 nM; 3 h) potently and selectively degrades BRD9 in G401 and HS-SY-II cells[1].
CW-3308 potently binds to purified BRD9 protein, with an IC50 of 5.0 nM[1].
CW-3308 (185 nM; 4 days) potently inhibits the viability of G401 and HS-SY-II cells, with IC50 values of 185 nM and 2.7 μM, respectively[1].

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

CW-3308 Related Antibodies

Western Blot Analysis[1]

Cell Line: G401 rhabdoid tumor cells
Concentration: 0, 0.1, 1, 10, 100, 1000 nM
Incubation Time: 3 h
Result: Reduced BRD9 protein levels by 30% at 0.1 nM, 68% at 1 nM, 90% at 10 nM, 93% at 100 nM, and 86% at 1000 nM.
No significant degradation of BRD7 or BRD4 was observed at any tested concentration.

Western Blot Analysis[1]

Cell Line: HS-SY-II synovial sarcoma cells
Concentration: 0, 0.1, 1, 10, 100, 1000 nM
Incubation Time: 3 h
Result: Reduced BRD9 protein levels by 16% at 1 nM, 70% at 10 nM, 98% at 100 nM, and 76% at 1000 nM.
No degradation was observed at 0.1 nM.

Western Blot Analysis[1]

Cell Line: G401 rhabdoid tumor cells
Concentration: 100 nM
Incubation Time: 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 h
Result: Reduced BRD9 protein levels by 77% at 0.5 h, 91% at 1 h, and ≥94% at all time points from 1.5 h to 4 h.

Cell Viability Assay[1]

Cell Line: G401 rhabdoid tumor cells
Concentration: 185 nM
Incubation Time: 4 days
Result: Inhibited cell growth with an IC50 of 185 nM and a maximum inhibition (Iₘₐₓ) of 90%.

Cell Viability Assay[1]

Cell Line: HS-SY-II synovial sarcoma cells
Concentration: 2.7 μM
Incubation Time: 4 days
Result: Inhibited cell growth with an IC50 of 2.7 μM and a maximum inhibition (Iₘₐₓ) of 94%.
Parmacokinetics
Species Dose Route AUC0-24 CL Vss Bioavailability Cmax T1/2
Mice[1] 3 mg/kg i.v. 991 ng·h/mL 48 mL/min/kg 18.2 L/kg 91 % / /
Mice[1] 5 mg/kg p.o. 1499 ng·h/mL / / 91 % 172 ng/mL 3.7 h
In Vivo

CW-3308 (25-50 mg/kg; p.o.; single administration / 5 days per week for 25 consecutive days) reduces BRD9 protein levels in HS-SY-II xenograft tumor tissues of SCID mice and inhibits the growth of HS-SY-II xenograft tumors[1].

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

Animal Model: SCID mice[1]
Dosage: 50 mg/kg/25, 50 mg/kg
Administration: p.o.; single dose/daily 5 days/week; 25 days
Result: Reduced BRD9 protein levels in tumor tissue by 92.5% relative to controls at 3 hours post-dose.
Reduced BRD9 protein levels in tumor tissue by 45% relative to controls at 24 hours post-dose.
Detected high drug concentrations in plasma and tumor tissue at 3 hours, with low concentrations present at 24 hours.
Achieved a maximum tumor growth inhibition (TGI) of 57% at 25 mg/kg.
Achieved a maximum tumor growth inhibition (TGI) of 60% at 50 mg/kg.
Observed no significant animal weight loss or other signs of toxicity during the study.
Molecular Weight

800.90

Formula

C45H48N6O8
CAS No.
Appearance

Solid

Color

White to light yellow

SMILES

O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=C4C(CN(CC(CC5)CCC65CCN(C(C7=C(OC)C=C(C(C8=CC=NC=C98)=CN(CC)C9=O)C=C7OC)=O)CC6)C4)=C3)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 4.17 mg/mL (5.21 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.2486 mL 6.2430 mL 12.4860 mL
5 mM 0.2497 mL 1.2486 mL 2.4972 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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In Vivo Dissolution Calculator
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
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Working solution concentration: mg/mL
Purity & Documentation

Purity: 99.43%

SDS (252 KB)

COA (246 KB) HNMR (496 KB) RP-HPLC (258 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.2486 mL 6.2430 mL 12.4860 mL 31.2149 mL
5 mM 0.2497 mL 1.2486 mL 2.4972 mL 6.2430 mL
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CW-3308 Related Classifications

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:

CW-33083055592-99-6CW3308CW 3308PROTACsEpigenetic Reader Domainmicexenograft tumor tissueHEK293 CRISPR knock-in cellsrhabdoid tumorG401 rhabdoid tumor cellssynovial sarcomaBRD4BRD9BRD7cereblonPROTACInhibitorinhibitorinhibit

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