Pelitrexol
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MedKoo CAT#: 202200

CAS#: 446022-33-9

Description: Pelitrexol is a GARFT inhibitor, and is also a water soluble antifolate with anti-proliferative activity. Pelitrexol inhibits activity of glycinamide ribonucleotide formyltransferase (GARFT), the first folate-dependent enzyme of the de novo purine synthesis pathway essential for cell proliferation. Enzyme inhibition reduces the purine nucleotides pool required for DNA replication and RNA transcription. As a result, this agent causes cell cycle arrest in S-phase, and ultimately inhibits tumor cell proliferation.

Chemical Structure

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Pelitrexol
CAS# 446022-33-9
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 202200
Name: Pelitrexol
CAS#: 446022-33-9
Chemical Formula: C20H25N5O6S
Exact Mass: 463.15
Molecular Weight: 463.510
Elemental Analysis: C, 51.83; H, 5.44; N, 15.11; O, 20.71; S, 6.92

Price and Availability

Size Price Availability Quantity
2mg USD 210 Ready to ship
5mg USD 450 Ready to ship
10mg USD 650 Ready to ship
25mg USD 950 Ready to ship
50mg USD 1650 Ready to ship
100mg USD 2850 Ready to ship
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Synonym: AG-2037; AG 2037; AG2037; Pelitrexol.

IUPAC/Chemical Name: (S)-2-(5-(2-((S)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl)ethyl)-4-methylthiophene-2-carboxamido)pentanedioic acid

InChi Key: QXOPTIPQEVJERB-JQWIXIFHSA-N

InChi Code: InChI=1S/C20H25N5O6S/c1-9-6-14(18(29)23-12(19(30)31)3-5-15(26)27)32-13(9)4-2-10-7-11-16(22-8-10)24-20(21)25-17(11)28/h6,10,12H,2-5,7-8H2,1H3,(H,23,29)(H,26,27)(H,30,31)(H4,21,22,24,25,28)/t10-,12-/m0/s1

SMILES Code: O=C(O)[C@@H](NC(C1=CC(C)=C(CC[C@H](CN2)CC3=C2N=C(N)NC3=O)S1)=O)CCC(O)=O

Appearance: white 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, not in water

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: Pelitrexol (AG 2037) is an inhibitor of glycinamide ribonucleotide formyltransferase (GARFT).
In vitro activity: To further define the effect of AG2037 on Rheb function, myc-tagged Rheb was immunoprecipitated from HEK293T cells treated with AG2037 with a conformation-specific monoclonal antibody that selectively recognizes RhebGTP. The results showed that AG2037 treatment dramatically decreased the ratio of RhebGTP to total Rheb and concomitantly suppressed S6RP and S6K1 phosphorylation (Figure 5B). Again, supplementation of the culture medium with adenine or guanine abrogated the negative effect of AG2037 on RhebGTP abundance in these cells (Figure 5B). AG2037 treatment consistently led to an upward shift in Rheb mobility during SDS-PAGE (Figure 5A). Reference: Cell Rep. 2017 Jun 27;19(13):2665-2680. https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(17)30685-X
In vivo activity: Mice harboring established, subcutaneous A427 xenografts were treated with either vehicle or AG2037 via intraperitoneal injection. Tumor growth was markedly reduced in the drug-treated animals relative to the vehicle-treated controls (Figure 4E). Tumor growth was suppressed by 64% and 69% at the 10 mg/kg and 20 mg/kg dosage levels, respectively. In a parallel group of tumor-bearing mice, the effect of AG2037 (20 mg/kg) on mTORC1 signaling 24 hr was assessed after the last drug administration. Immunoblot analyses of excised tumor tissue extracts revealed that AG2037 administration profoundly inhibited mTORC1-dependent phosphorylation of S6K1, S6RP, and CAD (Figure 4F). Thus, inhibition of GARFT-dependent purine biosynthesis blocks mTORC1 functions in this tumor cell line under both tissue culture and in vivo growth conditions. Reference: Cell Rep. 2017 Jun 27;19(13):2665-2680. https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(17)30685-X

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 53.90

Preparing Stock Solutions

The following data is based on the product molecular weight 463.51 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. Emmanuel N, Ragunathan S, Shan Q, Wang F, Giannakou A, Huser N, Jin G, Myers J, Abraham RT, Unsal-Kacmaz K. Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase. Cell Rep. 2017 Jun 27;19(13):2665-2680. doi: 10.1016/j.celrep.2017.05.043. PMID: 28658616.
In vivo protocol: 1. Emmanuel N, Ragunathan S, Shan Q, Wang F, Giannakou A, Huser N, Jin G, Myers J, Abraham RT, Unsal-Kacmaz K. Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase. Cell Rep. 2017 Jun 27;19(13):2665-2680. doi: 10.1016/j.celrep.2017.05.043. PMID: 28658616.

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