PHT-7.3 | CAS#1614225-93-2 | Ras 1 (Cnk1) inhibitor

MedKoo Cat#: 462416 | Name: PHT-7.3

Featured

Description:

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

PHT-7.3 is a selective inhibitor of connector enhancer of kinase suppressor of Ras 1 (Cnk1) pleckstrin homology (PH) domain, which inhibits mut-KRas, but not wild-type KRas cancer cell and tumor growth and signaling.

Chemical Structure

PHT-7.3

CAS#1614225-93-2

Theoretical Analysis

MedKoo Cat#: 462416

Name: PHT-7.3

CAS#: 1614225-93-2

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 730.00	2 Weeks
10mg	USD 1,040.00	2 Weeks
50mg	USD 2,300.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

PHT-7.3; PHT 7.3; PHT7.3

IUPAC/Chemical Name

4-((1,3-dioxan-2-yl)methyl)-2-((4-(p-tolyl)thiazol-2-yl)methyl)phthalazin-1(2H)-one

InChi Key

AFPMVLVIYVAFSP-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H23N3O3S/c1-16-7-9-17(10-8-16)21-15-31-22(25-21)14-27-24(28)19-6-3-2-5-18(19)20(26-27)13-23-29-11-4-12-30-23/h2-3,5-10,15,23H,4,11-14H2,1H3

SMILES Code

O=C1C2=C(C=CC=C2)C(CC3OCCCO3)=NN1CC4=NC(C5=CC=C(C)C=C5)=CS4

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

Instruction

View handling instruction

Biological target:

PHT-7.3 is a selective inhibitor of connector enhancer of kinase suppressor of Ras 1 (Cnk1) pleckstrin homology (PH) domain (Kd=4.7 μM).

In vitro activity:

PHT 7.0 and analogs 7.3 and 7.10 (Table 1) were tested in a small group of mut-KRas cells and found to inhibit cell proliferation (Figures S5). PHT-7.3 was the most consistently active (Figure S6), and was chosen for further study. Using 3D anchorage independent growth all the mut-KRas lines were sensitive to PHT-7.3 with IC50s averaging 4.4 μM, and as low as 0.3 μM (Figure 4B). Thus, treatment with PHT-7.3 mimics the growth and signaling effects of deletion of mut-KRas and Cnk1 knockdown, and displays a preferential growth inhibition of mut-KRas cell lines over wt-KRAS lines that is enhanced in anchorage independent conditions. Reference: Cancer Res. 2019 Jun 15;79(12):3100-3111. https://pubmed.ncbi.nlm.nih.gov/31040156/

In vivo activity:

PHT-7.3 demonstrated the desirable qualities of binding to the PH domain of Cnk1, selective inhibition of mut-KRas NSCLC cell growth and signaling, good in vivo pharmacokinetic properties, and was selected as a probe compound for further in vivo evaluation. This study tested PHT-7.3 for antitumor activity, and when dosed daily at 200 mg/kg ip for up to 20 days, PHT-7.3 exhibited cytostatic antitumor activity in the mut-KRas(G12S) A549 xenograft and mut-KRasG12V H441 xenograft (Figures 5A and and5B)5B) but not in the wt-KRas H1975 NSCLC xenograft (Figure 5C). Reference: Cancer Res. 2019 Jun 15;79(12):3100-3111. https://pubmed.ncbi.nlm.nih.gov/31040156/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	62.5	144.17

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 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:

Indarte M, Puentes R, Maruggi M, Ihle NT, Grandjean G, Scott M, Ahmed Z, Meuillet EJ, Zang S, Lemos R Jr, Du-Cuny L, Layng FIAL, Correa RG, Bankston LA, Liddington RC, Kirkpatrick L, Powis G. An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors. Cancer Res. 2019 Jun 15;79(12):3100-3111. doi: 10.1158/0008-5472.CAN-18-2372. Epub 2019 Apr 30. Erratum in: Cancer Res. 2019 Oct 15;79(20):5457. PMID: 31040156; PMCID: PMC6571060.

In vitro protocol:

In vivo protocol:

1: Indarte M, Puentes R, Maruggi M, et al. An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors [published correction appears in Cancer Res. 2019 Oct 15;79(20):5457]. Cancer Res. 2019;79(12):3100-3111. doi:10.1158/0008-5472.CAN-18-2372

View History

Phosphomolybdic acid

MedKoo CAT#: 533964

CAS#: 51429-74-4