NCT-503
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MedKoo CAT#: 407371

CAS#: 1916571-90-8

Description: 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

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NCT-503
CAS# 1916571-90-8

Theoretical Analysis

MedKoo Cat#: 407371
Name: NCT-503
CAS#: 1916571-90-8
Chemical Formula: C20H23F3N4S
Exact Mass: 408.16
Molecular Weight: 408.487
Elemental Analysis: C, 58.81; H, 5.68; F, 13.95; N, 13.72; S, 7.85

Price and Availability

Size Price Availability Quantity
10mg USD 120 Same day
25mg USD 250 Same day
50mg USD 450 Same day
100mg USD 750 Same day
200mg USD 1250 Same day
500mg USD 3650 Same day
1g USD 3850 Same day
2g USD 6450 2 Weeks
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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:

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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 50.0 122.41

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.

Recalculate based on batch purity %
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.

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