Cat. No.: HY-168162

ZLC491

고객리뷰

Based on 1 Customer Validation

ZLC491 is an orally active PROTAC degrader that selectively targets CDK12/CDK13 and exhibits certain oral bioavailability. ZLC491 induces cereblon- and proteasome-dependent selective degradation of CDK12 and CDK13. ZLC491 inhibits the transcription and expression of long genes, and mainly acts on a subset of DNA damage response genes. ZLC491 inhibits the proliferation of various triple-negative breast cancer cells. ZLC491 can be used in research related to triple-negative breast cancer.
(Pink: CDK12 and CDK13 ligand (HY-168163); Blue: Cereblon ligand (HY-W093272); Black: linker (HY-W904851)).

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

Purity: 98.51%
CAS No.: 3053716-46-1
화학식: C₄₈H₅₁FN₁₀O₅
분자량:866.98

보관:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

ZLC491 Chemical Structure

CAS No.: 3053716-46-1

사이즈

가격

재고

수량

Amount: USD 0.00

* 장바구니에 담기 전 물품의 수량을 선택해 주십시오.

Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
용액&용해도
- In Vitro
- In Vivo
순도&문서
References
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

ZLC491 is an orally active PROTAC degrader that selectively targets CDK12/CDK13 and exhibits certain oral bioavailability. ZLC491 induces cereblon- and proteasome-dependent selective degradation of CDK12 and CDK13. ZLC491 inhibits the transcription and expression of long genes, and mainly acts on a subset of DNA damage response genes. ZLC491 inhibits the proliferation of various triple-negative breast cancer cells. ZLC491 can be used in research related to triple-negative breast cancer^[1]^[2]. (Pink: CDK12 and CDK13 ligand (HY-168163); Blue: Cereblon ligand (HY-W093272); Black: linker (HY-W904851)).

IC₅₀ & Target

Cereblon

CDK12

CDK13

All PROTACs Isoforms :

All CDK Isoforms :

In Vitro

ZLC491 selectively inhibits the proliferation of triple-negative breast cancer (TNBC) cell lines MDA-MB-231, HCC38 and MDA-MB-436, with IC₅₀ values of 0.62, 0.19 and 0.12 μM after 5 days of treatment, respectively. It exerts a synergistic effect when combined with Cisplatin (HY-17394) or Olaparib (HY-10162). Meanwhile, ZLC491 shows extremely low activity against non-cancer cell lines^[1].
ZLC491 (0.01-3 μM; 4-15 h) degrades CDK12 and CDK13 in MDA-MB-231 cells in a dose- and time-dependent manner, with a DC₅₀ of 32 nM and 28 nM, respectively^[1].
ZLC491 (0.1-0.5 μM; 48 h) dose-dependently reduces the protein levels of DDR-related proteins ATM, BRCA1 and RAD51 in MDA-MB-231 cells^[1].
ZLC491 (60-300 nM; 12 h) potently and concentration-dependently inhibits the transcription of DDR genes in MDA-MB-231 cells, with no significant effect on the non-target gene ROR1^[1].

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

Western Blot Analysis^[1]

Cell Line:

HCC38, MDA-MB-436
Concentration:

0.01-3 μM
Incubation Time:

15 h
Result:

Concentration-dependently depleted CDK12 and CDK13 protein levels in both HCC38 and MDA-MB-436 cells, with robust degradation observed at concentrations ≥0.1 μM.

Western Blot Analysis^[1]

Cell Line:

MDA-MB-231
Concentration:

0.1-0.5 μM
Incubation Time:

48 h
Result:

Dose-dependently reduced protein levels of DDR-associated proteins ATM, BRCA1, and RAD51, concurrent with degradation of CDK12 and CDK13. Nearly eliminated CDK13 protein levels and significantly reduced ATM, BRCA1, and RAD51 levels relative to DMSO control at 0.5 μM.

Real Time qPCR^[1]

Cell Line:

MDA-MB-231
Concentration:

60-300 nM
Incubation Time:

12 h
Result:

Concentration-dependently suppressed transcription of DDR genes including ATM, ATR, BRCA1, BRCA2, FANCD2, and SMARCC. Showed no significant effect on the control gene ROR1. Reduced ATM, ATR, BRCA1, BRCA2, and FANCD2 mRNA levels to ≤20% of DMSO control at 300 nM.

Cell Proliferation Assay^[1]

Cell Line:

MDA-MB-231
Concentration:

0.3-7.5 μM (in combination with cisplatin or olaparib)
Incubation Time:

5 days
Result:

Demonstrated strong synergistic antiproliferative activity with cisplatin, with CI values of 0.17 for 1.5 μM ZLC491 + 25 μM cisplatin and 0.07 for 7.5 μM ZLC491 + 25 μM cisplatin.
Showed additive to synergistic activity with olaparib, with CI values of 0.90 for 1.5 μM ZLC491 + 25 μM Olaparib and 0.85 for 7.5 μM ZLC491 + 25 μM Olaparib.

Parmacokinetics

Species	Dose	Route	T_1/2	C_max	AUC_0-t	Bioavailability	CL
Mice^[1]	2.5 mg/kg	i.v.	2.46 h	4586.27 ng/mL	6815.36 ng·h/mL	/	6.38 mL/min/kg
Mice^[1]	10 mg/kg	p.o.	2.92 h	1309.81 ng/mL	12759.01 ng·h/mL	46.80 %	/

In Vivo

ZLC491 (200 mg/kg; p.o.; consecutive daily administration for 5 days) induces tumor cell apoptosis in vivo and is well tolerated in CB17SCID mice bearing MDA-MB-231 xenografts^[1].

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

Animal Model:

CB17SCID mice with Triple-negative breast cancer (female, 6−8 weeks old, orthotopic xenograft model)^[1]
Dosage:

100 mg/kg; 200 mg/kg
Administration:

p.o.; daily; 5 consecutive days
Result:

Significantly reduced tumor CDK12 and CDK13 protein levels relative to vehicle control at 100 mg/kg.
Achieved an even greater reduction in tumor CDK12 and CDK13 protein levels at 200 mg/kg.
Induced marked tumor cell apoptosis with a histology score of ~15 (vs. ~3 for vehicle) at 200 mg/kg.
Caused no body weight loss in treated mice.

Chemical Information

CAS No. 3053716-46-1
Appearance Solid
분자량 866.98
화학식 C₄₈H₅₁FN₁₀O₅
Color Light yellow to yellow
SMILES

O=C(N([C@@H]1CC[C@H](CC1)NC2=CC=C(C=N2)C#N)C3=CC=C(C=C3)N4CCN(CC4)C5CCN(CC5)C6=CC7=C(C=C6F)C(N(C7=O)C8CCC(NC8=O)=O)=O)NCC9=CC=CC=C9
선적

Room temperature in continental US; may vary elsewhere.

보관

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

용액&용해도

In Vitro:

DMSO : 100 mg/mL (115.34 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1534 mL

5.7671 mL

11.5343 mL

5 mM

0.2307 mL

1.1534 mL

2.3069 mL

10 mM

0.1153 mL

0.5767 mL

1.1534 mL

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.

몰농도 계산기

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

농도 희석 계산기

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (2.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (277 KB)
SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Zhou L, et al. Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader. J Med Chem. 2024;67(20):18247-18264. [Content Brief]

[2]. Tian X, et al. Degradation of Cyclin-Dependent Kinase: A New Weapon for Cancer Therapy[J]. Pharmaceutical Fronts, 2025.

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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	1.1534 mL	5.7671 mL	11.5343 mL	28.8357 mL
	5 mM	0.2307 mL	1.1534 mL	2.3069 mL	5.7671 mL
	10 mM	0.1153 mL	0.5767 mL	1.1534 mL	2.8836 mL
	15 mM	0.0769 mL	0.3845 mL	0.7690 mL	1.9224 mL
	20 mM	0.0577 mL	0.2884 mL	0.5767 mL	1.4418 mL
	25 mM	0.0461 mL	0.2307 mL	0.4614 mL	1.1534 mL
	30 mM	0.0384 mL	0.1922 mL	0.3845 mL	0.9612 mL
	40 mM	0.0288 mL	0.1442 mL	0.2884 mL	0.7209 mL
	50 mM	0.0231 mL	0.1153 mL	0.2307 mL	0.5767 mL
	60 mM	0.0192 mL	0.0961 mL	0.1922 mL	0.4806 mL
	80 mM	0.0144 mL	0.0721 mL	0.1442 mL	0.3604 mL
	100 mM	0.0115 mL	0.0577 mL	0.1153 mL	0.2884 mL

Keywords

상품명:
Cat. No.:
수량:
MCE Japan Authorized Agent:

상품명:
CAS No.:
Species:
Purity:
수량:

ZLC491

Cell Cycle/DNA Damage Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Orally Active Compound Library

Anti-Breast Cancer Compound Library

Anti-Blood Cancer Compound Library

PROTAC Library

Anti-Hematopathy Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

All PROTACs Isoforms

All CDK Isoforms

Biological Activity

Chemical Information

용액&용해도

순도&문서

References

Help & FAQs

Complete Stock Solution Preparation Table

ZLC491

Cell Cycle/DNA Damage Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Orally Active Compound Library

Anti-Breast Cancer Compound Library

Anti-Blood Cancer Compound Library

PROTAC Library

Anti-Hematopathy Compound Library

Multi-Target Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Protein Kinase Compound Library

Cell Proliferation Compound Library

High-Throughput Bioactive Compound Library

All PROTACs Isoforms

All CDK Isoforms

Biological Activity

Chemical Information

용액&용해도

순도&문서

References

Help & FAQs

Complete Stock Solution Preparation Table

ZLC491 Related Classifications

HY-168162 Related Classifications