PeptideDB

Talotrexin (PT523) 113857-87-7

Talotrexin (PT523) 113857-87-7

CAS No.: 113857-87-7

Talotrexin (PT523) is an analog of Aminopterin , a non-polyglutamic acid classical antifolate. Talotrexin is a specific
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Talotrexin (PT523) is an analog of Aminopterin , a non-polyglutamic acid classical antifolate. Talotrexin is a specific inhibitor of RFC (reduced folate carrier) that selectively inhibits RFC transport. Talotrexin shows anti-tumor activity by inhibiting tumor growth by targeting DHFR.

Physicochemical Properties


Molecular Formula C27H27N9O6
Molecular Weight 573.56
Exact Mass 573.208
CAS # 113857-87-7
PubChem CID 130731
Appearance Light yellow to yellow solid powder
Density 1.51g/cm3
Index of Refraction 1.737
LogP 3.304
Hydrogen Bond Donor Count 7
Hydrogen Bond Acceptor Count 13
Rotatable Bond Count 12
Heavy Atom Count 42
Complexity 949
Defined Atom Stereocenter Count 1
SMILES

O=C(O)[C@@H](NC(C1=CC=C(NCC2=NC3=C(NC(N=C3N=C2)=N)N)C=C1)=O)CCCNC(C4=CC=CC=C4C(O)=O)=O

InChi Key NYQPLPNEESYGNO-IBGZPJMESA-N
InChi Code

InChI=1S/C27H27N9O6/c28-21-20-22(36-27(29)35-21)32-13-16(33-20)12-31-15-9-7-14(8-10-15)23(37)34-19(26(41)42)6-3-11-30-24(38)17-4-1-2-5-18(17)25(39)40/h1-2,4-5,7-10,13,19,31H,3,6,11-12H2,(H,30,38)(H,34,37)(H,39,40)(H,41,42)(H4,28,29,32,35,36)/t19-/m0/s1
Chemical Name

2-[[(4S)-4-carboxy-4-[[4-[(2,4-diaminopteridin-6-yl)methylamino]benzoyl]amino]butyl]carbamoyl]benzoic acid
HS Tariff Code 2934.99.9001
Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity


ln Vitro Talotrexin exhibits negligible inhibitory action against PCFT or FRα [1]. The growth of R1-11/Tet-on-RFC HeLa cells is inhibited by talotrexin (1-1000 nM) [2].
ln Vivo The growth of mice A549 tumors is inhibited by talotrexin (0-35 mg/kg, intravenously administered once a week for 4 weeks) either alone or in combination with Paclitaxel (HY-B0015, 7.5 mg/kg) [2].
Animal Protocol Animal/Disease Models: NSCLC xenografts in athymic female nude mice (6-8 weeks)[2]
Doses: 15, 25, and 35 mg/kg, combined with Paclitaxel (HY-B0015, 7.5 mg/kg)
Route of Administration: IV injection, once weekly for 4 weeks
Experimental Results: Inhibited A549 tumor growth.
References

[1]. Folate transporter dynamics and therapy with classic and tumor-targeted antifolates. Sci Rep. 2021 Mar 18;11(1):6389.

[2]. Combination talotrexin (PT-523) with paclitaxel in A549 non-small cell lung cancer (NSCLC) athymic nude mice xenografts. Cancer Research, 2007, 67(1_Annual_Meeting).

Additional Infomation Talotrexin is an antimetabolite analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.
Drug Indication
Investigated for use/treatment in solid tumors, lung cancer, leukemia (unspecified), and leukemia (lymphoid).

Solubility Data


Solubility (In Vitro) May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
Solubility (In Vivo) Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300:Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)

Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.7435 mL 8.7175 mL 17.4350 mL
5 mM 0.3487 mL 1.7435 mL 3.4870 mL
10 mM 0.1743 mL 0.8717 mL 1.7435 mL
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.