Cat. No.: HY-101966

NCT-503

32 Cited Publications

고객리뷰

Based on 32 publication(s) in Google Scholar

NCT-503 is a blood-brain barrier-permeable, non-competitive PHGDH inhibitor with an IC₅₀ of 2.5 μM against human PHGDH. NCT-503 reduces glucose-derived serine production and the incorporation of one-carbon units into nucleotides without decreasing PHGDH protein expression. NCT-503 prevents high selenium-induced insulin resistance in mice by regulating blood glucose and insulin levels and improving glucose tolerance, and also inhibits the growth of tumors overexpressing PHGDH. NCT-503 can be used in research related to insulin resistance and breast cancer.

연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.

Purity: 99.69%
CAS No.: 1916571-90-8
화학식: C₂₀H₂₃F₃N₄S
분자량:408.48

보관:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

NCT-503 Chemical Structure

CAS No.: 1916571-90-8

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- 제품 설명
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (32)
용액&용해도
- In Vitro
- In Vivo
순도&문서
References
Help & FAQs
Classifications
Bioz

Biological Activity

제품 설명

IC₅₀ & Target

IC50: 2.5 μM (PHGDH)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
MDA-MB-231	IC₅₀	8 μM Compound: 31; NCT-503	Antiproliferative activity against human MDA-MB-231 cells overexpressing PHGDH assessed as reduction in cell growth Antiproliferative activity against human MDA-MB-231 cells overexpressing PHGDH assessed as reduction in cell growth	[PMID: 39106658]
MDA-MB-468	EC₅₀	8 μM Compound: 31; NCT-503	Cytotoxicity against human MDA-MB-468 cells Cytotoxicity against human MDA-MB-468 cells	[PMID: 29555419]

In Vitro

NCT-503 (10 μM; 1 h pretreatment, 4 h/24 h tracer incubation) engages PHGDH in MDA-MB-468 cells, reducing glucose-derived serine synthesis, impairing one-carbon unit incorporation into nucleotides from both endogenous and exogenous serine, and increasing SHMT1-mediated one-carbon unit wasting; the C234S PHGDH^G12C mutant reduces NCT-503 potency by ~3-fold^[2].
NCT-503 (dose-response concentrations; 4 days) selectively inhibits the viability of PHGDH-dependent human cancer cell lines (MDA-MB-468, BT-20, HCC70, HT1080, MT-3) with EC₅₀ values of 8-16 μM, while showing minimal to no toxicity towards PHGDH-independent cell lines^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay^[2]

Cell Line:

PHGDH-dependent (MDA-MB-468, BT-20, HCC70, HT1080, MT-3) and PHGDH-independent (MDA-MB-231, ZR-75-1, SK-MEL-2) human cancer cell lines
Concentration:

Dose-response concentrations
Incubation Time:

4 days
Result:

Exhibited EC₅₀ values of 8-16 μM for PHGDH-dependent cell lines.
Showed a 6- to 10-fold higher EC₅₀ for MDA-MB-231 cells.
Showed no toxicity towards other PHGDH-independent cell lines.

In Vivo

NCT-503 (30 mg/kg; i.p.; twice weekly; 5 months) effectively prevents high-selenium-induced insulin resistance in male C57BL/6J mice, as evidenced by normalized fasting blood glucose, improved glucose tolerance and insulin sensitivity, reduced plasma insulin levels, and restored PI3K-AKT-mTOR pathway activity in pancreatic tissue, while potently inhibiting PHGDH enzyme activity across liver, muscle, and pancreas tissues^[1].
NCT-503 (40 mg/kg; i.p.; daily; 24 days) selectively inhibits growth and induces necrosis in PHGDH-dependent MDA-MB-468 orthotopic breast cancer xenografts in NOD.CB17-Prkdc^scid/J mice without causing weight loss^[2].
NCT-503 (30 mg/kg; i.p.; single dose) engages PHGDH in MDA-MB-468 orthotopic xenografts, reducing glucose-derived serine synthesis^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6J (male, 4 weeks old, SPF status, high-selenium diet-induced insulin resistance model)^[1]
Dosage:

30 mg/kg
Administration:

i.p.; twice weekly; 5 months
Result:

Significantly reduced high-selenium-induced weight gain compared to the high-selenium alone group, with final body weight closer to the adequate-selenium control group.
Prevented the gradual increase in fasting blood glucose levels seen in the high-selenium alone group, with levels remaining near those of the adequate-selenium control group by the fifth month.
Improved glucose tolerance, with significantly lower blood glucose levels compared to the high-selenium alone group during the glucose tolerance test.
Improved insulin sensitivity, with a reduced percentage change in blood glucose following insulin injection compared to the high-selenium alone group.
Significantly reduced plasma insulin levels compared to the high-selenium alone group.
Significantly increased plasma homocysteine levels compared to the high-selenium alone group.
Significantly reduced plasma serine levels compared to the high-selenium alone group.
Markedly reduced PHGDH enzyme activity in the liver, muscle, and pancreas compared to the high-selenium alone group; PHGDH activity was also significantly lower than in the adequate-selenium control group and the high-selenium + serine group.
Significantly reduced GPX1 and SELENOP protein expression in the liver compared to the high-selenium alone group and the high-selenium + serine group.
Significantly reduced GPX1 and SELENON protein expression in the muscle compared to the high-selenium alone group and the high-selenium + serine group.
Significantly reduced GPX1 protein expression in the pancreas compared to the high-selenium alone group and the high-selenium + serine group.
Increased PHGDH protein expression in the liver, muscle, and pancreas compared to the high-selenium + serine group.
Significantly increased SHMT1 protein expression in the pancreas compared to the high-selenium + serine group.
Significantly increased mTOR protein expression in the pancreas compared to the high-selenium alone group.
Significantly increased phosphorylated Akt (Ser-473 and Thr-308) protein expression in the pancreas compared to the high-selenium alone group.

Animal Model:

NOD.CB17-Prkdcscid/J (female, 6-8 weeks old, orthotopic xenograft via injection of 500,000 MDA-MB-468 cells into the 4th mammary fat pad)^[2]
Dosage:

40 mg/kg
Administration:

i.p.; daily; 24 days
Result:

Reduced the growth and weight of PHGDH-dependent MDA-MB-468 xenografts.
Selectively increased necrosis in these xenografts.
Decreased production of glucose-derived serine in tumors.
Reached ~3 μM tumor exposure at the end of the experiment.
Prevented weight loss in mice during the 24-day treatment period.

Chemical Information

CAS No. 1916571-90-8
Appearance Solid
분자량 408.48
화학식 C₂₀H₂₃F₃N₄S
Color Off-white to light yellow
SMILES

S=C(N1CCN(CC2=CC=C(C(F)(F)F)C=C2)CC1)NC3=NC(C)=CC(C)=C3
선적

Room temperature in continental US; may vary elsewhere.

보관

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (32)

All WBCell Proliferation/Viability AssayRT-PCRIn Vivo Efficacy Study

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Journal Impact Factor

Nature

Ageing promotes metastasis via activation of the integrated stress response. [Abstract]

2026 Apr;652(8112):1339-1348. PMID: 41813904
Cell Res

Comprehensive metabolomics expands precision medicine for triple-negative breast cancer. [Abstract]

2022 May;32(5):477-490. PMID: 35105939
Immunity

Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease. [Abstract]

2021 Aug 10;54(8):1728-1744.e7. PMID: 34343498
Nat Metab

The alternative activity of nuclear PHGDH contributes to tumour growth under nutrient stress. [Abstract]

2021 Oct;3(10):1357-1371. PMID: 34663976

NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371. [Abstract]

SW1990 cells expressing the indicated Flag–c-Jun were pretreated with NCT-503 (40 μM) and were cultured in glucose-free DMEM for 12 h.

NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371. [Abstract]

Cells pretreated with or without NCT-503 (40 μM) were cultured in normal or glucose-free DMEM for 36 h Cellular viability was examined by CCK-8 assay

NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371. [Abstract]

Cells pretreated with or without NCT-503 (40 μM) were cultured in normal or glucose-free DMEM for 24 h. mRNA levels of potential c-Jun target genes were analysed by real-time PCR.

NCT-503 purchased from MedChemExpress. Usage Cited in: Nat Metab. 2021 Oct;3(10):1357-1371. [Abstract]

A total of 1 × 10⁷ SW1990 cells expressing the indicated sgRNAs were subcutaneously injected into athymic nude mice. NCT-503 (40 mg/kg/day; i.p.) administration in mice 7 d after subcutaneous injection of tumour cells. Representative tumour xenografts (left) and quantification of tumour volumes (middle) are shown; lysates were collected from SW1990 cells that were cultured for 6 h in glucose-free DMEM and from tumour tissues, then immunoprecipitated c-Jun was subjected to immunoblotting analyses (right).
Cancer Res

Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression. [Abstract]

2021 Mar 15;81(6):1443-1456. PMID: 33500247
Autophagy

Porcine reproductive and respiratory syndrome virus hijacks the non-canonical enzymatic function of PHGDH to arrest autophagic flux for viral replication. [Abstract]

2026 Jun 16:1-20. PMID: 42260976
Nat Commun

Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer. [Abstract]

2019 Jun 20;10(1):2701. PMID: 31221965
Redox Biol

Central carbon metabolism exhibits unique characteristics during the handling of fungal patterns by monocyte-derived dendritic cells. [Abstract]

2024 Jul:73:103187. PMID: 38744190
Mol Cell

Metabolic profiling reveals pyrimidine synthesis enzyme CAD as a central carbon metabolism signaling node in cancer cell proliferation. [Abstract]

2026 Apr 16;86(8):1529-1545.e7. PMID: 41950920
Mol Cell

One-Carbon Metabolism Supports S-Adenosylmethionine and Histone Methylation to Drive Inflammatory Macrophages. [Abstract]

2019 Sep 19;75(6):1147-1160.e5. PMID: 31420217
J Exp Clin Cancer Res

PHGDH activation fuels glioblastoma progression and radioresistance via serine synthesis pathway. [Abstract]

2025 Mar 19;44(1):99. PMID: 40102981
J Clin Invest

Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression. [Abstract]

2020 Jun 1;130(6):3253-3269. PMID: 32478681
Cell Rep Med

Targeting the noncanonical function of metabolic enzyme PHGDH in driving PD-L1 expression and cancer immune evasion. [Abstract]

2026 Mar 26:102704. PMID: 41905348
Cell Commun Signal

FOXC1-mediated serine metabolism reprogramming enhances colorectal cancer growth and 5-FU resistance under serine restriction. [Abstract]

2025 Jan 7;23(1):13. PMID: 39773485
J Cachexia Sarcopenia Muscle

Skeletal muscle hypertrophy rewires glucose metabolism: An experimental investigation and systematic review. [Abstract]

2024 Jun;15(3):989-1002. PMID: 38742477
Int J Biol Macromol

Acetylation-modified phosphoglycerate dehydrogenase is associated with enhanced serine biosynthesis and one‑carbon metabolism, supporting heat resistance in Pleurotus ostreatus. [Abstract]

2026 Jun 25:373:153200. PMID: 42349591
Cell Prolif

PHGDH Orchestrates Cell Cycle Progression to Drive Cardiomyocyte Proliferation and Myocardial Regeneration via TGF-β/Smad Signalling Pathway. [Abstract]

2025 Sep 10:e70123. PMID: 40930719
J Agric Food Chem

Ethyl Acetate Fraction of Zanthoxylum bungeanum Ameliorates Cognitive Deficit by Facilitating the PHGDH-Dependent Astrocyte-Neuron Serine Shuttle in Aging Mice. [Abstract]

2025 Jul 2;73(26):16301-16316. PMID: 40537930
Nutrients

The Inhibitory Effects of NCT503 and Exogenous Serine on High-Selenium Induced Insulin Resistance in Mice. [Abstract]

2025 Jan 16;17(2):311. PMID: 39861441
Biol Direct

PHGDH mediated serine biosynthesis metabolism suppresses vascular calcification. [Abstract]

2026 Mar 23;21(1):57. PMID: 41872929
Am J Physiol Cell Physiol

Glycolytic metabolism and biomass production from glucose in human skeletal muscle growth. [Abstract]

2025 Nov 1;329(5):C1560-C1576. PMID: 41071646
J Nutr Biochem

L-serine dose-dependently ameliorates high-selenium-induced insulin resistance in mice. [Abstract]

2026 May 30:157:110432. PMID: 42218944
J Virol

Newcastle Disease Virus Manipulates Mitochondrial MTHFD2-Mediated Nucleotide Metabolism for Virus Replication. [Abstract]

2023 Mar 30;97(3):e0001623. PMID: 36794935

NCT-503 purchased from MedChemExpress. Usage Cited in: J Virol. 2023 Mar 30;97(3):e0001623. [Abstract]

NCT-503 (2.5, 5, 10 µM) blocks serine synthesis but promotes a compensatory upregulation of MTHFD2 in Newcastle disease virus (NDV)-infected cells.
Lab Invest

Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O6-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma. [Abstract]

2022 Feb;102(2):194-203. PMID: 34625658
Br J Haematol

Phosphoglycerate dehydrogenase promotes proliferation and bortezomib resistance through increasing reduced glutathione synthesis in multiple myeloma. [Abstract]

2020 Jul;190(1):52-66. PMID: 32037523
Biotechnol Bioprocess Eng

2025 Dec 8.
Chem Zvesti

2020 May.
Onco Targets Ther

Inhibition of Serine Metabolism Promotes Resistance to Cisplatin in Gastric Cancer. [Abstract]

2020 May 29;13:4833-4842. PMID: 32581546
bioRxiv

2025 July 02.
Chalmers University of Technology

2024.
bioRxiv

2024 July 05.
bioRxiv

2023 Aug 22.

용액&용해도

In Vitro:

DMSO : 50 mg/mL (122.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Ethanol : 13.33 mg/mL (32.63 mM; ultrasonic and warming and heat to 60°C)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.4481 mL

12.2405 mL

24.4810 mL

5 mM

0.4896 mL

2.4481 mL

4.8962 mL

10 mM

0.2448 mL

1.2241 mL

2.4481 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

몰농도 계산기

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

농도 희석 계산기

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: 2.5 mg/mL (6.12 mM); Suspended solution; Need ultrasonic

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (6.12 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Working Solution

For the following dissolution methods, please prepare the working solution directly:

It is recommended to prepare fresh solutions and use them promptly within a short period of time.

The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 50% PEG300 50% Saline

Solubility: 10 mg/mL (24.48 mM); Suspended solution; Need ultrasonic

Protocol 2

Add each solvent one by one: 0.5% Methylcellulose/0.2% Tween-80 in Saline water

Solubility: 2 mg/mL (4.90 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

순도&문서

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Zhan S, et al. The Inhibitory Effects of NCT503 and Exogenous Serine on High-Selenium Induced Insulin Resistance in Mice. Nutrients. 2025;17(2):311. Published 2025 Jan 16. [Content Brief]

[2]. Pacold ME, et al. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016;12(6):452-458. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
Ethanol / DMSO	1 mM	2.4481 mL	12.2405 mL	24.4810 mL	61.2025 mL
	5 mM	0.4896 mL	2.4481 mL	4.8962 mL	12.2405 mL
	10 mM	0.2448 mL	1.2241 mL	2.4481 mL	6.1203 mL
	15 mM	0.1632 mL	0.8160 mL	1.6321 mL	4.0802 mL
	20 mM	0.1224 mL	0.6120 mL	1.2241 mL	3.0601 mL
	25 mM	0.0979 mL	0.4896 mL	0.9792 mL	2.4481 mL
	30 mM	0.0816 mL	0.4080 mL	0.8160 mL	2.0401 mL
DMSO	40 mM	0.0612 mL	0.3060 mL	0.6120 mL	1.5301 mL
	50 mM	0.0490 mL	0.2448 mL	0.4896 mL	1.2241 mL
	60 mM	0.0408 mL	0.2040 mL	0.4080 mL	1.0200 mL
	80 mM	0.0306 mL	0.1530 mL	0.3060 mL	0.7650 mL
	100 mM	0.0245 mL	0.1224 mL	0.2448 mL	0.6120 mL

Keywords

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NCT-503

Anti-diabetic Compound Library

Anti-Cancer Metabolism Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Metabolic Enzyme Compound Library

Anti-Drug-Resistant Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Metabolism/Protease Compound Library

Anti-Cancer Compound Library

CNS-Penetrant Compound Library

Publications Citing Use of MedChemExpress (MCE) NCT-503

Biological Activity

Chemical Information

Publications (32)

용액&용해도

순도&문서

References

Help & FAQs

Complete Stock Solution Preparation Table

NCT-503

Anti-diabetic Compound Library

Anti-Cancer Metabolism Compound Library

Targeted Diversity Library

Heterocyclic Compound Library

Metabolic Enzyme Compound Library

Anti-Drug-Resistant Compound Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Metabolism/Protease Compound Library

Anti-Cancer Compound Library

CNS-Penetrant Compound Library

Publications Citing Use of MedChemExpress (MCE) NCT-503

Biological Activity

Chemical Information

Publications (32)

용액&용해도

순도&문서

References

Help & FAQs

Complete Stock Solution Preparation Table

NCT-503 Related Classifications

HY-101966 Related Classifications