製品番号: HY-168162

ZLC491

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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)).

商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。

純度: 98.51%
CAS 番号: 3053716-46-1
分子式: C₄₈H₅₁FN₁₀O₅
分子量:866.98

保管条件:

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

ZLC491 構造式

CAS 番号: 3053716-46-1

容量

価格（税別）

在庫状況

数量

Amount: USD 0.00

* アイテムを追加する前、数量をご選択ください

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Use of MCE Products

Fluorescent Dye

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

生物活性
- 製品説明
- IC₅₀ & Target
- 体外実験
- Parmacokinetics
- 体内実験
化学情報
溶剤 & 溶解度
- 体外
- 体内
純度とドキュメンテーション
参考文献
Help & FAQs
関連分類
Bioz

生物活性

製品説明

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

PROTACs アイソフォーム固有の製品をすべて表示 :

CDK アイソフォーム固有の製品をすべて表示 :

体外実験

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 %	/

体内実験

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.

化学情報

CAS 番号 3053716-46-1
性状 Solid
分子量 866.98
分子式 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
輸送条件

Room temperature in continental US; may vary elsewhere.

保管条件

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

溶剤 & 溶解度

体外:

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.

モル濃度計算機

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

Mass Mass

濃度濃度

体積体積

分子量分子量

希釈計算機

濃度 _(開始) × 体積 _(開始) = 濃度 _(終了) × 体積 _(終了)

濃度 _(開始) 濃度 _(開始)

体積 _(開始) 体積 _(開始)

濃度 _(終了) 濃度 _(終了)

体積 _(終了) 体積 _(終了)

体内:

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

純度とドキュメンテーション

バッチを選択:

純度: 99.98%

Assay: 99.98%

ee.: 99.98%

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COA (2659 KB)
元素分析報告書 (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)
取扱説明書 (2659 KB)

参考文献

[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

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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

PROTACs アイソフォーム固有の製品をすべて表示

CDK アイソフォーム固有の製品をすべて表示

生物活性

化学情報

溶剤 & 溶解度

純度とドキュメンテーション

参考文献

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

PROTACs アイソフォーム固有の製品をすべて表示

CDK アイソフォーム固有の製品をすべて表示

生物活性

化学情報

溶剤 & 溶解度

純度とドキュメンテーション

参考文献

Help & FAQs

Complete Stock Solution Preparation Table

ZLC491 関連分類

HY-168162 関連分類