HTH-01-015

• CAS: 1613724-42-7
• Catalog Number: ACM1613724427
• Category: Inhibitors
• Molecular Weight: 468.57
• Molecular Formula: C26H28N8O
• Description: HTH-01-015 is a potent and selective inhibitor of NUAK1 (IC50 = 100 nM) and does not affect the activity of a panel of 139 other kinases, including additional AMPK family members. The administration of HTH-01-015 to MEFs (mouse embryonic fibroblasts) significantly inhibits migration in a wound-healing assay to a similar extent as NUAK1-knockout. HTH-01-015 also inhibit proliferation of MEFs to the same extent as NUAK1 knockout and U2OS cells to the same extent as NUAK1 shRNA knockdown. HTH-01-015 impaired the invasive potential of U2OS cells in a 3D cell invasion assay to the same extent as NUAK1 knockdown. HTH-01-015 will serve as useful chemical probes to delineate the biological roles of the NUAK kinases.
• Synonyms: HTH-01-015; HTH01-015; HTH 01-015; HTH-01015; HTH01015; HTH 01015
• IUPAC Name: 4,5,13-trimethyl-2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5,13-dihydro-6H-naphtho[2,3-e]pyrimido[5,4-b][1,4]diazepin-6-one
• Canonical SMILES: CC1=C(N(C)C(C2=CC(C=CC=C3)=C3C=C2N4C)=O)C4=NC(NC5=CN(N=C5)C6CCNCC6)=N1
• InChI: InChI=1S/C26H28N8O/c1-16-23-24(31-26(29-16)30-19-14-28-34(15-19)20-8-10-27-11-9-20)32(2)22-13-18-7-5-4-6-17(18)12-21(22)25(35)33(23)3/h4-7,12-15,20,27H,8-11H2,1-3H3,(H,29,30,31)
• InChI Key: CHSDJDLAKKAWCI-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: HTH-01-015 is a selective NUAK1/ARK5 inhibitor (IC50 is 100 nM). HTH-01-015 inhibits NUAK1 with >100-fold higher potency than NUAK2 (IC50 of >10 μM).
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 66.65; H, 6.02; N, 23.91; O, 3.41
• Exact Mass: 468.2386
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: In both cases, the PTEN- cell lines were more sensitive to HTH-01-015 than their PTEN+ counterparts (Fig. 5b). Therefore, this study concluded that HTH-01-015 selectively targeted PTEN- cell lines and inhibition of NUAK1 has broad PTEN-SSL activity.; Reference: Breast Cancer Res. 2018 Mar 22;20(1):22. https://pubmed.ncbi.nlm.nih.gov/29566768/
• In Vivo Activity: Administration of WZ4003 and HTH-01-015 to MEFs (mouse embryonic fibroblasts) significantly inhibits migration in a wound-healing assay to a similar extent as NUAK1-knockout. WZ4003 and HTH-01-015 also inhibit proliferation of MEFs to the same extent as NUAK1 knockout and U2OS cells to the same extent as NUAK1 shRNA knockdown. This study found that WZ4003 and HTH-01-015 impaired the invasive potential of U2OS cells in a 3D cell invasion assay to the same extent as NUAK1 knockdown. The results of the present study indicate that WZ4003 and HTH-01-015 will serve as useful chemical probes to delineate the biological roles of the NUAK kinases.; Reference: Biochem J. 2014 Jan 1;457(1):215-25. https://pubmed.ncbi.nlm.nih.gov/24171924/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).