HTH-01-015 | CAS#1613724-42-7 | NUAK1 inhibitor

MedKoo Cat#: 406832 | Name: HTH-01-015

Description:

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

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.

Chemical Structure

HTH-01-015

CAS#1613724-42-7

Theoretical Analysis

MedKoo Cat#: 406832

Name: HTH-01-015

CAS#: 1613724-42-7

Chemical Formula: C26H28N8O

Exact Mass: 468.2386

Molecular Weight: 468.57

Elemental Analysis: C, 66.65; H, 6.02; N, 23.91; O, 3.41

Price and Availability

Size	Price	Availability
10mg	USD 150.00	2 Weeks
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 1,950.00	2 Weeks
1g	USD 3,250.00	2 Weeks

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Synonym

HTH-01-015; HTH01-015; HTH 01-015; HTH-01015; HTH01015; HTH 01015.

IUPAC/Chemical 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

InChi Key

CHSDJDLAKKAWCI-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

CC1=C(N(C)C(C2=CC(C=CC=C3)=C3C=C2N4C)=O)C4=NC(NC5=CN(N=C5)C6CCNCC6)=N1

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

>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

Product Data

Product Data

Instruction

View handling instruction

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).

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/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	64.03
	DMSO	67.5	143.98
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.07
	Ethanol	38.0	80.99

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 468.57 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. Tang YC, Ho SC, Tan E, Ng AWT, McPherson JR, Goh GYL, Teh BT, Bard F, Rozen SG. Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer. Breast Cancer Res. 2018 Mar 22;20(1):22. doi: 10.1186/s13058-018-0949-3. PMID: 29566768; PMCID: PMC5863852. 2. Banerjee S, Zagórska A, Deak M, Campbell DG, Prescott AR, Alessi DR. Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase. Biochem J. 2014 Jul 15;461(2):233-45. doi: 10.1042/BJ20140408. PMID: 24785407; PMCID: PMC4109838. 3. Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PMID: 24171924; PMCID: PMC3969223.

In vitro protocol:

In vivo protocol:

1. Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PMID: 24171924; PMCID: PMC3969223.

1: Banerjee S, Zagórska A, Deak M, Campbell DG, Prescott AR, Alessi DR. Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase. Biochem J. 2014 Jul 15;461(2):233-45. doi: 10.1042/BJ20140408. PubMed PMID: 24785407; PubMed Central PMCID: PMC4109838. 2: Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 1;457(1):215-25. doi: 10.1042/BJ20131152. PubMed PMID: 24171924; PubMed Central PMCID: PMC3969223.