NCT-502 | CAS#1542213-00-2 | PHGDH inhibitor

MedKoo Cat#: 561459 | Name: NCT-502

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Description:

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

NCT-502 is an inhibitor of human 3-phosphoglycerate dehydrogenase (PHGDH). NCT-502 reduces the production of glucose-derived serine in cells and suppresses the growth of PHGDH-dependent cancer cells in culture and in orthotopic xenograft tumors.

Chemical Structure

NCT-502

CAS#1542213-00-2

Theoretical Analysis

MedKoo Cat#: 561459

Name: NCT-502

CAS#: 1542213-00-2

Chemical Formula: C18H20F3N5S

Exact Mass: 395.1392

Molecular Weight: 395.45

Elemental Analysis: C, 54.67; H, 5.10; F, 14.41; N, 17.71; S, 8.11

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 220.00
10mg	USD 375.00
25mg	USD 730.00

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Related CAS #

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Synonym

NCT-502; NCT 502; NCT502;

IUPAC/Chemical Name

N-(4,6-Dimethylpyridin-2-yl)-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-carbothioamide

InChi Key

HHKPPMSUPATMKP-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H20F3N5S/c1-12-9-13(2)23-15(10-12)24-17(27)26-7-5-25(6-8-26)16-4-3-14(11-22-16)18(19,20)21/h3-4,9-11H,5-8H2,1-2H3,(H,23,24,27)

SMILES Code

S=C(N1CCN(C2=NC=C(C(F)(F)F)C=C2)CC1)NC3=NC(C)=CC(C)=C3

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:

NCT-502 is a human phosphoglycerate dehydrogenase (PHGDH) inhibitor, cytotoxic to PHGDH-dependent cancer cells, and reduces glucose-derived serine production, with an IC50 of 3.7 μM against PHGDH.

In vitro activity:

As previously reported, NCT-502 (27) and NCT-503 (31) reduced the production of glucose-derived serine in cells and suppressed the growth of PHGDH-dependent cancer cells, both in culture and in orthotopic xenograft tumors. The metabolic effects of these molecules were found to be largely specific to PHGDH and downstream pathways linked to serine flux. However, NCT-502 (27) inhibitor treatment was found to reduce aspartate levels in cells, irrespective of PHGDH levels; decreased oxygen consumption was observed in the presence of both active and inactive representatives of this chemotype, suggesting the effect may be driven in part by electron transport chain inhibition. Reference: Bioorg Med Chem. 2018 May 1;26(8):1727-1739. https://pubmed.ncbi.nlm.nih.gov/29555419/

In vivo activity:

For this, NCT-502 or vehicle control (PBS) was injected intratumorally every three days after tumor injection, and then subcutaneous xenografts were peeled off after 4 weeks. The results showed that the xenografts in the NCT-502-injected mouse group were significantly smaller compared to those displayed by the vehicle group (Figure (Figure5B-D).5B-D). Reference: Int J Biol Sci. 2022 Aug 29;18(14):5459-5474. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9461664/

	Solvent	mg/mL	mM
Solubility
	DMF	25.0	63.22
	DMSO	70.0	177.01
	Ethanol	1.0	2.53
	Ethanol:PBS (pH 7.2) (1:10)	0.3	0.83

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 395.45 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. Rohde JM, Brimacombe KR, Liu L, Pacold ME, Yasgar A, Cheff DM, Lee TD, Rai G, Baljinnyam B, Li Z, Simeonov A, Hall MD, Shen M, Sabatini DM, Boxer MB. Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors. Bioorg Med Chem. 2018 May 1;26(8):1727-1739. doi: 10.1016/j.bmc.2018.02.016. Epub 2018 Feb 27. PMID: 29555419; PMCID: PMC5891386. 2. Shen L, Zhang J, Zheng Z, Yang F, Liu S, Wu Y, Chen Y, Xu T, Mao S, Yan Y, Li W, Zhang W, Yao X. PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer. Int J Biol Sci. 2022 Aug 29;18(14):5459-5474. doi: 10.7150/ijbs.74546. PMID: 36147463; PMCID: PMC9461664.

In vitro protocol:

In vivo protocol:

1. Shen L, Zhang J, Zheng Z, Yang F, Liu S, Wu Y, Chen Y, Xu T, Mao S, Yan Y, Li W, Zhang W, Yao X. PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer. Int J Biol Sci. 2022 Aug 29;18(14):5459-5474. doi: 10.7150/ijbs.74546. PMID: 36147463; PMCID: PMC9461664.

1: Pacold, M.E.,Brimacombe, K.R.,Chan, S.H., et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nature Chemical Biology 12(6), 452-458 (2016).