WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H401535
CAS#: 934593-90-5
Description: CAY10585, also known as LW6, was first identified and reported by a group scientists from Korea. LW8 was found to inhibits the accumulation of HIF-1alpha. LW6 decreased HIF-1alpha protein expression without affecting HIF-1beta expression. It was further found that LW8 promoted the degradation of wild type HIF-1alpha, but not of a DM-HIF-1alpha with modifications of P402A and P564A, at hydroxylation sites in the oxygen-dependent degradation domain (ODDD). LW6 did not affect the activity of prolyl hydroxylase (PHD), but induced the expression of von Hippel-Lindau (VHL), which interacts with prolyl-hydroxylated HIF-1alpha for proteasomal degradation. In the presence of LW8, knockdown of VHL did not abolish HIF-1alpha protein accumulation, indicating that LW8 degraded HIF-1alpha via regulation of VHL expression. In mice carrying xenografts of human colon cancer HCT116 cells, LW8 demonstrated strong anti-tumor efficacy in vivo and caused a decrease in HIF-1alpha expression in frozen-tissue immunohistochemical staining. These data suggest that LW8 may be valuable in the development of a HIF-1alpha inhibitor for cancer treatment. (source: Biochem Pharmacol. 2010 Oct 1;80(7):982-9.)
Hodoodo Cat#: H401535
Name: CAY10585
CAS#: 934593-90-5
Chemical Formula: C26H29NO5
Exact Mass: 435.20
Molecular Weight: 435.512
Elemental Analysis: C, 71.70; H, 6.71; N, 3.22; O, 18.37
Synonym: CAY10585; CAY-10585; CAY 10585; LW6; LW-6; LW 6
IUPAC/Chemical Name: methyl 3-(2-(4-(adamantan-1-yl)phenoxy)acetamido)-4-hydroxybenzoate
InChi Key: BJRPPNOJYFZSLY-UHFFFAOYSA-N
InChi Code: InChI=1S/C26H29NO5/c1-31-25(30)19-2-7-23(28)22(11-19)27-24(29)15-32-21-5-3-20(4-6-21)26-12-16-8-17(13-26)10-18(9-16)14-26/h2-7,11,16-18,28H,8-10,12-15H2,1H3,(H,27,29)
SMILES Code: O=C(OC)C1=CC=C(O)C(NC(COC2=CC=C(C34CC5CC(C4)CC(C5)C3)C=C2)=O)=C1
Appearance: white 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, not in water
Shelf Life: >2 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:
| Biological target: | LW6 (HIF-1α inhibitor) is a novel HIF-1 inhibitor with an IC50 of 4.4 μM. |
| In vitro activity: | Here is a summary of the reported in vitro activity data for CAY10585 (LW6) as a HIF-1α inhibitor: HIF-1α Inhibition: LW6 reduces HIF-1α protein levels in various cancer cell lines under hypoxic conditions. Reported IC50 values for HIF-1α inhibition range from 3 to 10 μM in different cell models. Cell Viability and Anti-Proliferative Effects: LW6 exhibits cytotoxic effects in hypoxia-dependent cancer cell models. IC50 values for cell viability reduction in certain cancer cell lines: HCT116 (colon cancer cells): ~8.2 μM A549 (lung cancer cells): ~6.5 μM HeLa (cervical cancer cells): ~5.1 μM Downregulation of HIF-1 Target Genes: LW6 significantly decreases VEGF (vascular endothelial growth factor) expression, a key downstream target of HIF-1α. In some studies, LW6 reduced VEGF mRNA expression by more than 50% in hypoxic conditions. Induction of Cell Death and Apoptosis: LW6 induces apoptosis in cancer cells, possibly through mitochondrial pathway activation and ROS (reactive oxygen species) generation. Increased levels of cleaved caspase-3 and PARP cleavage have been observed, indicating apoptosis induction. Selectivity: LW6 preferentially inhibits cell growth under hypoxic conditions, with less cytotoxicity under normoxic conditions. |
| In vivo activity: | The objective of this study was to investigate the pharmacokinetics and metabolism of LW6 in male ICR mice to support its preclinical development as an antitumor agent. After i.v. administration of LW6 at a dose of 5 mg/kg, the plasma concentration declined rapidly in an apparent polyexponential fashion. The plasma level of LW6 was below the quantitation limit beyond 4 h (Figure 1A). An apparent terminal phase was defined in the plasma concentration-time curve of LW6 between 1 to 4 h postadministration with a t1/2 of 0.6 ± 0.1 h (Figure 1 and Table 1); the volume of distribution at steady state (Vss) was 0.5 ± 0.1 L/kg, close to the total body water volume (0.7 L/kg), indicating that LW6 was distributed outside the vasculature. The systemic clearance (CL) of LW6 was 1.7 ± 0.1 L/hr/kg (Table 1), lower than the hepatic blood flow of the mouse (Table 1). LW6 (1 µM) was incubated with pooled mouse liver microsomes (0.5 mg/mL) in the absence or presence of NADPH (1 mM) to determine its conversion to APA. LW6 was degraded slowly in the absence or presence of NADPH, with 63% or 65% remaining after 60 min microsomal incubations, respectively (Figure 3A). LW6 was converted slowly to APA (t1/2 > 60 min) in a quantitative manner in liver microsomes (Figure 3A). APA, following its formation, gradually disappeared from the microsomal incubation media only in the presence of NAPDH (Figure 3A). To determine whether APA was metabolized by cytochrome P450 (CYP450), APA (1 µM) also was incubated with pooled male mouse liver microsomes (0.5 mg/mL) in the absence or presence of NADPH (1 mM). As shown in Figure 4, APA was progressively decreased when incubated with mouse liver microsomes in the presence of NADPH. These results suggested that LW6 was metabolized to APA, which was further metabolized by CYP450. In the case of mouse serum, LW6 was also converted slowly to APA (Figure 3B). These results suggested that LW6 as an anticancer drug is highly likely to work as its active metabolite APA in the body. Molecules. 2021 Apr; 26(8): 2226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070284/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 17.5 | 40.18 | |
| DMF | 25.6 | 58.80 |
The following data is based on the product molecular weight 435.51 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. Zhang X, Kumstel S, Jiang K, Meng S, Gong P, Vollmar B, Zechner D. LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer. J Adv Res. 2019 Apr 24;20:9-21. doi: 10.1016/j.jare.2019.04.006. PMID: 31193017; PMCID: PMC6514270. 2. Sato M, Hirose K, Kashiwakura I, Aoki M, Kawaguchi H, Hatayama Y, Akimoto H, Narita Y, Takai Y. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 2015 Sep;12(3):3462-3468. doi: 10.3892/mmr.2015.3862. Epub 2015 May 27. PMID: 26017562; PMCID: PMC4526100. 3. Lee K, Kang JE, Park SK, Jin Y, Chung KS, Kim HM, Lee K, Kang MR, Lee MK, Song KB, Yang EG, Lee JJ, Won M. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9. doi: 10.1016/j.bcp.2010.06.018. Epub 2010 Jun 23. PMID: 20599784. 4. Lee JY, Lee K, Lee K, Kang JS, Kim MJ, Yoo DG, Kim JA, Shin EJ, Oh SJ. Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice. Molecules. 2021 Apr 12;26(8):2226. doi: 10.3390/molecules26082226. PMID: 33921487; PMCID: PMC8070284. |
| In vitro protocol: | 1. Zhang X, Kumstel S, Jiang K, Meng S, Gong P, Vollmar B, Zechner D. LW6 enhances chemosensitivity to gemcitabine and inhibits autophagic flux in pancreatic cancer. J Adv Res. 2019 Apr 24;20:9-21. doi: 10.1016/j.jare.2019.04.006. PMID: 31193017; PMCID: PMC6514270. 2. Sato M, Hirose K, Kashiwakura I, Aoki M, Kawaguchi H, Hatayama Y, Akimoto H, Narita Y, Takai Y. LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 2015 Sep;12(3):3462-3468. doi: 10.3892/mmr.2015.3862. Epub 2015 May 27. PMID: 26017562; PMCID: PMC4526100. |
| In vivo protocol: | 1. Lee K, Kang JE, Park SK, Jin Y, Chung KS, Kim HM, Lee K, Kang MR, Lee MK, Song KB, Yang EG, Lee JJ, Won M. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9. doi: 10.1016/j.bcp.2010.06.018. Epub 2010 Jun 23. PMID: 20599784. 2. Lee JY, Lee K, Lee K, Kang JS, Kim MJ, Yoo DG, Kim JA, Shin EJ, Oh SJ. Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice. Molecules. 2021 Apr 12;26(8):2226. doi: 10.3390/molecules26082226. PMID: 33921487; PMCID: PMC8070284. |
1: Lee K, Kang JE, Park SK, Jin Y, Chung KS, Kim HM, Lee K, Kang MR, Lee MK, Song KB, Yang EG, Lee JJ, Won M. LW6, a novel HIF-1 inhibitor, promotes proteasomal degradation of HIF-1alpha via upregulation of VHL in a colon cancer cell line. Biochem Pharmacol. 2010 Oct 1;80(7):982-9. Epub 2010 Jun 23. PubMed PMID: 20599784.
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