ZLDI-8 | CAS#667880-38-8 | ADAM-17 inhibitor

MedKoo Cat#: 462439 | Name: ZLDI-8

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ZLDI-8 is a Notch activating/cleaving enzyme ADAM-17 inhibitor and inhibits the cleavage of Notch protein. ZLDI-8 decreases the expression of pro-survival/anti-apoptosis and epithelial-mesenchymal transition (EMT) related proteins. ZLDI-8 is also a competitive and irreversible tyrosine phosphatase (Lyp) inhibitor.

Chemical Structure

ZLDI-8

CAS#667880-38-8

Theoretical Analysis

MedKoo Cat#: 462439

Name: ZLDI-8

CAS#: 667880-38-8

Chemical Formula: C24H23N3O3S

Exact Mass: 433.1460

Molecular Weight: 433.53

Elemental Analysis: C, 66.49; H, 5.35; N, 9.69; O, 11.07; S, 7.40

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 2,050.00	Ready to ship
500mg	USD 3,650.00	Ready to ship

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Related CAS #

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Synonym

ZLDI-8; ZLDI8; ZLDI 8

IUPAC/Chemical Name

5-((1-(2-(2,4-dimethylphenoxy)ethyl)-2-methyl-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

InChi Key

GNBZGGYWSRGVBG-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H23N3O3S/c1-14-8-9-21(15(2)12-14)30-11-10-27-16(3)18(17-6-4-5-7-20(17)27)13-19-22(28)25-24(31)26-23(19)29/h4-9,12-13H,10-11H2,1-3H3,(H2,25,26,28,29,31)

SMILES Code

O=C(/C(C(N1)=O)=C/C2=C(C)N(CCOC3=CC=C(C)C=C3C)C4=C2C=CC=C4)NC1=S

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C23R10B09

QC Data

View QC data: current batch, Lot#C23R10B09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ZLDI-8 is also a competitive and irreversible tyrosine phosphatase (Lyp) inhibitor with an IC50 of 31.6 μM and a Ki of 26.22 μM. ZLDI-8 inhibits the growth of MHCC97-H cells with an IC50 of 5.32 μM.

In vitro activity:

ZLDI-8 is a potential candidate for improving colorectal cancer (CRC) treatment outcomes. ZLDI-8 demonstrated specific inhibition of CRC cell proliferation by targeting ADAM17 and the Notch pathway. ZLDI-8 showed promising potential as a chemosensitizer, enhancing the anti-tumor and anti-metastasis effects of chemotherapy drugs, such as 5-fluorouracil and irinotecan, by reversing Notch and epithelial-mesenchymal transition (EMT) pathways. Reference: Cell Prolif. 2018 Oct;51(5):e12480. https://pubmed.ncbi.nlm.nih.gov/30069943/

In vivo activity:

ZLDI-8 has potential as an effective agent in the treatment of drug-resistant lung cancer. ZLDI-8 suppressed multidrug-resistant lung cancer xenograft growth and blocks metastasis in a tail vein injection mice model. Reference: Pharmacol Res. 2019 Oct;148:104406. https://pubmed.ncbi.nlm.nih.gov/31442576/

Preparing Stock Solutions

The following data is based on the product molecular weight 433.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Lu H, Wu C, Jiang XW, Zhao Q. ZLDI-8 suppresses angiogenesis and vasculogenic mimicry in drug-resistant NSCLC in vitro and in vivo. Lung Cancer. 2023 Aug;182:107279. doi: 10.1016/j.lungcan.2023.107279. Epub 2023 Jun 14. PMID: 37364397. 2. Li DD, Zhao CH, Ding HW, Wu Q, Ren TS, Wang J, Chen CQ, Zhao QC. A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo. Cell Prolif. 2018 Oct;51(5):e12480. doi: 10.1111/cpr.12480. Epub 2018 Aug 2. PMID: 30069943; PMCID: PMC6528951. 3. Lu HY, Chu HX, Tan YX, Qin XC, Liu MY, Li JD, Ren TS, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the metastasis of hepatocellular carcinoma by reversing epithelial-mesenchymal transition in vitro and in vivo. Life Sci. 2020 Mar 1;244:117343. doi: 10.1016/j.lfs.2020.117343. Epub 2020 Jan 21. PMID: 31978449. 4. Lu HY, Zu YX, Jiang XW, Sun XT, Liu TY, Li RL, Wu Q, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo. Pharmacol Res. 2019 Oct;148:104406. doi: 10.1016/j.phrs.2019.104406. Epub 2019 Aug 20. PMID: 31442576.

In vitro protocol:

In vivo protocol:

1. Lu HY, Chu HX, Tan YX, Qin XC, Liu MY, Li JD, Ren TS, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the metastasis of hepatocellular carcinoma by reversing epithelial-mesenchymal transition in vitro and in vivo. Life Sci. 2020 Mar 1;244:117343. doi: 10.1016/j.lfs.2020.117343. Epub 2020 Jan 21. PMID: 31978449. 2. Lu HY, Zu YX, Jiang XW, Sun XT, Liu TY, Li RL, Wu Q, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo. Pharmacol Res. 2019 Oct;148:104406. doi: 10.1016/j.phrs.2019.104406. Epub 2019 Aug 20. PMID: 31442576.

1: Xu C, Gao X, Ren T, Geng H, Yang K, Huang Y, Zhang W, Hou S, Song A, Zhang Y, Zhao Q. The ADAM17 inhibitor ZLDI-8 sensitized hepatocellular carcinoma cells to sorafenib through Notch1-integrin β-talk. Pharmacol Res. 2024 May;203:107142. doi: 10.1016/j.phrs.2024.107142. Epub 2024 Mar 24. PMID: 38522759. 2: Lu H, Wu C, Jiang XW, Zhao Q. ZLDI-8 suppresses angiogenesis and vasculogenic mimicry in drug-resistant NSCLC in vitro and in vivo. Lung Cancer. 2023 Aug;182:107279. doi: 10.1016/j.lungcan.2023.107279. Epub 2023 Jun 14. PMID: 37364397. 3: Zhang Y, Xu C, Xu X, Ma L, Li R, Xu Z, Zhao Q. Pharmacokinetics, tissue distribution, and antitumor activity of a novel compound, NY-2, in non-small cell lung cancer. Front Pharmacol. 2023 Jan 16;13:1074576. doi: 10.3389/fphar.2022.1074576. PMID: 36726788; PMCID: PMC9884808. 4: Roubtsova A, Garçon D, Lacoste S, Chamberland A, Marcinkiewicz J, Métivier R, Sotin T, Paquette M, Bernard S, Cariou B, Le May C, Koschinsky ML, Seidah NG, Prat A. PCSK9 deficiency results in a specific shedding of excess LDLR in female mice only: Role of hepatic cholesterol. Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Dec;1867(12):159217. doi: 10.1016/j.bbalip.2022.159217. Epub 2022 Aug 17. PMID: 35985474. 5: Lu HY, Chu HX, Tan YX, Qin XC, Liu MY, Li JD, Ren TS, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the metastasis of hepatocellular carcinoma by reversing epithelial-mesenchymal transition in vitro and in vivo. Life Sci. 2020 Mar 1;244:117343. doi: 10.1016/j.lfs.2020.117343. Epub 2020 Jan 21. PMID: 31978449. 6: Lu HY, Zu YX, Jiang XW, Sun XT, Liu TY, Li RL, Wu Q, Zhang YS, Zhao QC. Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo- resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo. Pharmacol Res. 2019 Oct;148:104406. doi: 10.1016/j.phrs.2019.104406. Epub 2019 Aug 20. PMID: 31442576. 7: Li DD, Zhao CH, Ding HW, Wu Q, Ren TS, Wang J, Chen CQ, Zhao QC. A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5-Fluorouracil by reversing Notch and epithelial-mesenchymal transition in vitro and in vivo. Cell Prolif. 2018 Oct;51(5):e12480. doi: 10.1111/cpr.12480. Epub 2018 Aug 2. PMID: 30069943; PMCID: PMC6528951. 8: Zhang Y, Li D, Jiang Q, Cao S, Sun H, Chai Y, Li X, Ren T, Yang R, Feng F, Li BA, Zhao Q. Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells. Cell Death Dis. 2018 Jul 3;9(7):743. doi: 10.1038/s41419-018-0804-6. PMID: 29970890; PMCID: PMC6030059.