NCT-503 | PHGDH inhibitor | CAS#1916571-90-8

MedKoo Cat#: 407371 | Name: NCT-503

Description:

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

NCT-503 is an inhibitor of 3-phosphoglycerate dehydrogenase (PHGDH), inhibiting serine synthesis from 3-phosphoglycerate in cells with an IC50 value of 2.5 µM.

Chemical Structure

NCT-503

CAS#1916571-90-8

Theoretical Analysis

MedKoo Cat#: 407371

Name: NCT-503

CAS#: 1916571-90-8

Chemical Formula: C20H23F3N4S

Exact Mass: 408.1596

Molecular Weight: 408.49

Elemental Analysis: C, 58.81; H, 5.68; F, 13.95; N, 13.72; S, 7.85

Price and Availability

Size	Price	Availability
10mg	USD 120.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 3,650.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	2 Weeks

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Related CAS #

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Synonym

NCT-503; NCT 503; NCT503.

IUPAC/Chemical Name

N-(4,6-dimethylpyridin-2-yl)-4-(4-(trifluoromethyl)benzyl)piperazine-1-carbothioamide

InChi Key

PJNSZIQUFLWRLH-UHFFFAOYSA-N

InChi Code

InChI=1S/C20H23F3N4S/c1-14-11-15(2)24-18(12-14)25-19(28)27-9-7-26(8-10-27)13-16-3-5-17(6-4-16)20(21,22)23/h3-6,11-12H,7-10,13H2,1-2H3,(H,24,25,28)

SMILES Code

S=C(N1CCN(CC2=CC=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

Certificate of Analysis

View CoA: current batch, Lot#C21R03B19

QC Data

View QC data: current batch, Lot#C21R03B19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NCT-503 is a phosphoglycerate dehydrogenase (PHGDH) inhibitor with an IC50 of 2.5 µM.

In vitro activity:

Human phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step in the canonical glucose-derived serine synthesis pathway. NCT-503, a PHGDH inhibitor, inhibits serine synthesis from 3-phosphoglycerate in cells (IC50=2.5 µM). NCT-503 is inactive against a panel of other dehydrogenases and shows minimal cross-reactivity in a panel of 168 GPCRs. Competition studies of NCT-503 against 3-phosphoglycerate (3-PG) and the co-substrate NAD+ reveal a non-competitive mode of inhibition with respect to both 3-PG and NAD+. NCT-503 has EC50s of 8–16 µM for the PHGDH-dependent cell lines, a 6- to 10-fold higher EC50 for MDA-MB-231 cells, and no toxicity towards other PHGDH-independent cell lines. Reference: Nat Chem Biol. 2016 Jun;12(6):452-8. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27110680/

In vivo activity:

NCT-503 exhibits favorable absorption, distribution, metabolism and excretion (ADME) properties. NCT-503 has good exposure, half-life (2.5 hr) and Cmax (20 µM in plasma) following intraperitoneal administration with significant partitioning into the liver and brain. NCT-503 treatment reduces the growth and weight of PHGDH-dependent MDA-MB-468 xenografts but does not affect the growth or weight of PHGDH-independent MDA-MB-231 xenografts. Reference: Nat Chem Biol. 2016 Jun;12(6):452-8. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27110680/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	122.41

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 408.49 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:

In vitro protocol:

1. Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, Cho S, Freinkman E, Birsoy K, Abu-Remaileh M, Shaul YD, Liu CM, Zhou M, Koh MJ, Chung H, Davidson SM, Luengo A, Wang AQ, Xu X, Yasgar A, Liu L, Rai G, Westover KD, Vander Heiden MG, Shen M, Gray NS, Boxer MB, Sabatini DM. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8. doi: 10.1038/nchembio.2070. Epub 2016 Apr 25. Erratum in: Nat Chem Biol. 2016 Jul 19;12 (8):656. PMID: 27110680; PMCID: PMC4871733. 2. 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.

In vivo protocol:

1. Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, Cho S, Freinkman E, Birsoy K, Abu-Remaileh M, Shaul YD, Liu CM, Zhou M, Koh MJ, Chung H, Davidson SM, Luengo A, Wang AQ, Xu X, Yasgar A, Liu L, Rai G, Westover KD, Vander Heiden MG, Shen M, Gray NS, Boxer MB, Sabatini DM. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 Jun;12(6):452-8. doi: 10.1038/nchembio.2070. Epub 2016 Apr 25. Erratum in: Nat Chem Biol. 2016 Jul 19;12 (8):656. PMID: 27110680; PMCID: PMC4871733. 2. Hamanaka RB, Nigdelioglu R, Meliton AY, Tian Y, Witt LJ, O'Leary E, Sun KA, Woods PS, Wu D, Ansbro B, Ard S, Rohde JM, Dulin NO, Guzy RD, Mutlu GM. Inhibition of Phosphoglycerate Dehydrogenase Attenuates Bleomycin-induced Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2018 May;58(5):585-593. doi: 10.1165/rcmb.2017-0186OC. PMID: 29019702; PMCID: PMC5946329.

1: Wang J, Zeng L, Wu N, Liang Y, Jin J, Fan M, Lai X, Chen ZS, Pan Y, Zeng F, Deng F. Inhibition of phosphoglycerate dehydrogenase induces ferroptosis and overcomes enzalutamide resistance in castration-resistant prostate cancer cells. Drug Resist Updat. 2023 Sep;70:100985. doi: 10.1016/j.drup.2023.100985. Epub 2023 Jun 14. PMID: 37423117. 2: Wei L, Lee D, Law CT, Zhang MS, Shen J, Chin DW, Zhang A, Tsang FH, Wong CL, Ng IO, Wong CC, Wong CM. Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC. Nat Commun. 2019 Oct 15;10(1):4681. doi: 10.1038/s41467-019-12606-7. PMID: 31615983; PMCID: PMC6794322. 3: Arlt B, Mastrobuoni G, Wuenschel J, Astrahantseff K, Eggert A, Kempa S, Deubzer HE. Inhibiting PHGDH with NCT-503 reroutes glucose-derived carbons into the TCA cycle, independently of its on-target effect. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1282-1289. doi: 10.1080/14756366.2021.1935917. PMID: 34192988; PMCID: PMC8253182. 4: Pralea IE, Moldovan RC, Țigu AB, Moldovan CS, Fischer-Fodor E, Iuga CA. Cellular Responses Induced by NCT-503 Treatment on Triple-Negative Breast Cancer Cell Lines: A Proteomics Approach. Biomedicines. 2024 May 14;12(5):1087. doi: 10.3390/biomedicines12051087. PMID: 38791048; PMCID: PMC11117597. 5: Elsaadi S, Steiro I, Abdollahi P, Vandsemb EN, Yang R, Slørdahl TS, Rø TB, Menu E, Sponaas AM, Børset M. Targeting phosphoglycerate dehydrogenase in multiple myeloma. Exp Hematol Oncol. 2021 Jan 4;10(1):3. doi: 10.1186/s40164-020-00196-w. PMID: 33397437; PMCID: PMC7784327. 6: Wang K, Lu H, Wang X, Liu Q, Hu J, Liu Y, Jin M, Kong D. Simultaneous suppression of PKM2 and PHGDH elicits synergistic anti-cancer effect in NSCLC. Front Pharmacol. 2023 May 22;14:1200538. doi: 10.3389/fphar.2023.1200538. PMID: 37284309; PMCID: PMC10239820. 7: He L, Liu Y, Liu D, Feng Y, Yin J, Zhou X. Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation. Oxid Med Cell Longev. 2021 Oct 19;2021:4232704. doi: 10.1155/2021/4232704. PMID: 34712382; PMCID: PMC8548146. 8: Ma Q, Gao S, Li C, Yao J, Xie Y, Jiang C, Yuan J, Fei K, Zhang P, Wang H, Li X. Cuproptosis and Serine Metabolism Blockade Triggered by Copper-Based Prussian Blue Nanomedicine for Enhanced Tumor Therapy. Small. 2025 Feb;21(5):e2406942. doi: 10.1002/smll.202406942. Epub 2024 Dec 15. PMID: 39676407. 9: Dewdney B, Alanazy M, Gillman R, Walker S, Wankell M, Qiao L, George J, Roberts A, Hebbard L. The effects of fructose and metabolic inhibition on hepatocellular carcinoma. Sci Rep. 2020 Oct 7;10(1):16769. doi: 10.1038/s41598-020-73653-5. PMID: 33028928; PMCID: PMC7541473. 10: Bojkova D, Reus P, Panosch L, Bechtel M, Rothenburger T, Kandler JD, Pfeiffer A, Wagner JUG, Shumliakivska M, Dimmeler S, Olmer R, Martin U, Vondran FWR, Toptan T, Rothweiler F, Zehner R, Rabenau HF, Osman KL, Pullan ST, Carroll MW, Stack R, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr. Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform. iScience. 2023 Feb 17;26(2):105944. doi: 10.1016/j.isci.2023.105944. Epub 2023 Jan 7. PMID: 36644320; PMCID: PMC9822553.