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DHFR inhibitor

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By Targets:	Dihydrofolate reductase (DHFR) (37) Akt (1) Antibiotic (5) Antifolate (39) Apoptosis (7) Autophagy (9) Bacterial (23) DNA/RNA Synthesis (3) EGFR (8) Endogenous Metabolite (1) Fungal (3) Isotope-Labeled Compounds (3) Nucleoside Antimetabolite/Analog (1) Parasite (17) VEGFR (2)
By Research Areas:	Cancer (38) Cardiovascular Disease (1) Infection (50) Inflammation/Immunology (6)
Click Chemistry:	Alkynes (1)

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Products

Isotope-Labeled Compounds

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Targets Recommended: Dihydrofolate reductase (DHFR)

Cat. No.	Product Name	Target	Research Areas	Chemical Structure

HY-153007

DHFR-IN-5	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-5 is a potent and orally active dihydrofolate reductase (DHFR) inhibitor with a K_i value of 0.54 nM for quadruple mutant Plasmodium falciparum DHFR. DHFR-IN-5 shows anti-malaria activity .

HY-W003561

DHFR-IN-3	Antifolate Parasite	Infection
DHFR-IN-3 is a dihydrofolate reductase (DHFR) inhibitor with the IC₅₀ values of 19 μM and 12 μM in rat liver and P. carinii DHFR, respectively .

HY-149699

DHFR-IN-12	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-12 (Compound 5c) is a *DHFR* inhibitor which has good antibacterial activity .

HY-162475

Fluorofolin	Dihydrofolate reductase (DHFR) Bacterial	Infection
Fluorofolin is a dihydrofolate reductase (DHFR) inhibitor with an IC₅₀ of 2.5 nM. Fluorofolin exhibits significant activity against P. aeruginosa .

HY-161064

DHFR-IN-15	Dihydrofolate reductase (DHFR)	Cancer
DHFR-IN-15 (compound 34) is a dihydrofolate reductase (DHFR) inhibitor with potential anticancer activity. DHFR-IN-15 effectively binds to DHFR in cells, reducing DHFR levels to 10 nM .

HY-163725

DHFR-IN-18	Dihydrofolate reductase (DHFR)	Cancer
DHFR-IN-18 (compound 19D) is a *DHFR* inhibitor. DHFR-IN-18 can be used in anti-leukemia research .

HY-156412

DHFR-IN-10	Bacterial	Infection
DHFR-IN-10 (compound 4c) is a potent *DHFR* inhibitor, with an IC₅₀ of 4.21 μM for M. tuberculosis DHFR enzyme. DHFR-IN-10 exhibits potent antituberculosis efficiency .

HY-153007A

DHFR-IN-5 hydrochloride	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-5 hydrochloride is a potent and orally active dihydrofolate reductase (DHFR) inhibitor with a K_i value of 0.54 nM for quadruple mutant Plasmodium falciparum DHFR. DHFR-IN-5 hydrochloride shows anti-malaria activity .

HY-156414

DHFR-IN-11	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-11 (compound 6b) is inhibitor of *DHFR, and has inhibitory potency versus M. tuberculosis* *DHFR* enzyme with IC₅₀ values 5.70 μM .

HY-161010

DHFR-IN-13	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-13 (Compd Hit8) is an active R. solani DHFR inhibitor with an IC₅₀ value of 10.2 μM. DHFR-IN-13 has selectivity of inhibition against human DHFR with an IC₅₀ value of 227.7 μM. DHFR-IN-13 also is a fungicide. DHFR-IN-13 has high antifungal activity against R. solani with EC₅₀ value of 38.2 mg/L .

HY-137439

Fanotaprim VYR-006	Antifolate	Infection
Fanotaprim is a dihydrofolate reductase *(DHFR)* inhibitor with IC₅₀s of 1.57 and 308 nM for tgDHFR (Toxoplasma gondii DHFR) and hDHFR (human DHFR), respectively. Fanotaprim has the potential for the research of toxoplasmosis .

HY-B1902

Diaveridine EGIS-5645	Antifolate Bacterial	Infection
Diaveridine (EGIS-5645) is a dihydrofolate reductase (DHFR) inhibitor with a K_i of 11.5 nM for the wild type DHFR and also an antibacterial agent.

HY-161063

DHFR-IN-14	Dihydrofolate reductase (DHFR)	Cancer
DHFR-IN-14 (compound 32) is a pyrimethamine (Pyr)-type, dihydrofolate reductase (DHFR) inhibitor with potential anticancer activity .

HY-151159

DHFR-IN-4	Dihydrofolate reductase (DHFR) EGFR	Cancer
DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with an IC₅₀ value of 123 nM. DHFR-IN-4 also has inhibitory activity against EGFR and HER2 with IC₅₀s of 246 nM and 357 nM, respectively. DHFR-IN-4 has remarkable broad spectrum cytotoxic potency against cancer cells .

HY-W587663

4′-DTMP	Dihydrofolate reductase (DHFR)	Infection
4 '-DTMP is a DHFR inhibitor with Ki of 5.1 nM (DHFR ^WT) and 34.3 nM (DHFR ^L28R), respectively. 4 '-DTMP carries a polar modification that induces additional local interactions with the enzyme. In particular, the hairpin structure on the M20 ring is related to the internal communication of the DHFR. 4 '-DTMP has potential inhibition of E.coli .

HY-143236

DHFR-IN-1	Bacterial Fungal	Infection
DHFR-IN-1 (compound 12) is a potent and selective *DHFR* (dihydrofolate reductase)inhibitor, with an IC₅₀ of 40.71 nM. DHFR-IN-1 exhibits promising antibacterial activity against gram-positive and gram-negative bacteria. DHFR-IN-1 exhibits moderate antifungal activities. DHFR-IN-1 exhibits a high synergistic effect with Levofloxacin (HY-B0330), where the FIC (fractional inhibitory concentration index) value is 0.249 .

HY-107033

Tetroxoprim HE 781	Antifolate	Infection Inflammation/Immunology
Tetroxoprim is an antimicrobial *DHFR* inhibitor .

HY-156122

DHFR-IN-8	Dihydrofolate reductase (DHFR) Bacterial	Infection
DHFR-IN-8 (compound 6r) is a dihydrofolate reductase (DHFR) inhibitor that affects purine and thymidylate biosynthesis in cell proliferation and growth. DHFR-IN-8 inhibits methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 (IC₅₀=15.6 ng/mL) in mouse models of systemic infection and thigh infection .

HY-161292

DHFR-IN-16	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-16 (compound 8d) is an inhibitor of dihydrofolate reductase (DHFR) (IC₅₀=0.199 μM) and can be used in anti-infectious research .

HY-163722

EGFR/DHFR-IN-1	EGFR Dihydrofolate reductase (DHFR)	Cancer
EGFR/DHFR-IN-1 (Compound 10e) is a dual inhibitor of EGFR and *DHFR* with IC₅₀s of 0.151 and 0.541 µM, respectively. EGFR/DHFR-IN-1 arrests the cell cycle at both G0-G1 and S phases .

HY-18062S

Pyrimethamine-d3	Antifolate Parasite	Infection
Pyrimethamine-d₃ is the deuterium labeled Pyrimethamine. Pyrimethamine is a medication used for protozoal infections; interferes with tetrahydrofolic acid synthesis from folic acid by inhibiting the enzyme dihydrofolate reductase (DHFR)[1][2].

HY-162656

DHFR-IN-19	Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-19 (Compound 2g) is a selective inhibitor for TbDHFR with K_i of 9 nM. DHFR-IN-19 exhibits antiparasitic activity against Trypanosoma brucei with an EC₅₀ of 14.5 μM .

HY-B1902R

Diaveridine (Standard)	Antifolate Bacterial	Infection
Diaveridine (Standard) is the analytical standard of Diaveridine. This product is intended for research and analytical applications. Diaveridine (EGIS-5645) is a dihydrofolate reductase (DHFR) inhibitor with a Ki of 11.5 nM for the wild type DHFR and also an antibacterial agent.

HY-149633

EGFR/HER2/DHFR-IN-3	EGFR Dihydrofolate reductase (DHFR) Apoptosis	Cancer
EGFR/HER2/DHFR-IN-3 (compound 4c) is a potent dual inhibitor of EGFR/HER2, with IC₅₀s of 0.138 and 0.092 μM, respectively. EGFR/HER2/DHFR-IN-3 also inhibits *DHFR, with an IC₅₀* of 0.193 M. EGFR/HER2/DHFR-IN-3 causes arrest at the S phase of the cell cycle and induces apoptosis in MCF7 breast cancer cells .

HY-147661

DHFR-IN-2	Antifolate	Infection
DHFR-IN-2 (compound 4e) is a potent and uncompetitive inhibitor for MtDHFR (dihydrofolate reductase from M. tuberculosis), with an IC₅₀ of 7 μM. DHFR-IN-2 can be used for tuberculosis (TB) research .

HY-139743

Aditoprime Aditoprim	Antifolate Bacterial	Infection
Aditoprime (Aditoprim), a selective bacterial dihydrofolate reductase (DHFR) inhibitor, inhibits the transformation of dihydrofolic acid to tetrahydrofolic acid. Aditoprime inhibits E.coli and L.casei DHFR with IC₅₀ of 47 and 520 nM, respectively. Aditoprime has a broad antimicrobial spectrum, good antibacterial activity and excellent pharmacokinetics .

HY-10373

Trimetrexate 1 Publications Verification CI-898	Dihydrofolate reductase (DHFR) Antibiotic Antifolate Parasite Bacterial DNA/RNA Synthesis	Infection Cancer
Trimetrexate (CI-898) is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC₅₀ values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate can also inhibit the growth of various cancer cells. Trimetrexate can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer .

HY-10373A

Trimetrexate trihydrochloride CI-898 trihydrochloride	Dihydrofolate reductase (DHFR) Antibiotic Antifolate Parasite Bacterial DNA/RNA Synthesis	Infection
Trimetrexate (CI-898) trihydrochloride is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC₅₀ values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate trihydrochloride can also inhibit the growth of various cancer cells. Trimetrexate trihydrochloride can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer .

HY-162358

DHFR-IN-17	Dihydrofolate reductase (DHFR) Bacterial	Infection
DHFR-IN-17 (compound j9) is an oral active SaDHFR inhibitor with the IC₅₀ of 0.97 nM. DHFR-IN-17 shows antibacterial activity against S. aureus with the minimum inhibitory concentration of 0.031 μg/mL .

HY-151459

VEGFR-2/DHFR-IN-2	VEGFR Bacterial Dihydrofolate reductase (DHFR) Fungal	Infection Cancer
VEGFR-2/DHFR-IN-2 (compound 5b) is an inhibitor of VEGFR-2 and *DHFR* with IC₅₀s of 0.623 and 9.085 μM, respectively. VEGFR-2/DHFR-IN-2 exhibits good cytotoxic activities against C26, HepG2, and MCF7 cancer cell lines with IC₅₀ values of 3.59-8.38 μM. VEGFR-2/DHFR-IN-2 can be used for the research of cancer .

HY-149200

Lysine-methotrexate	Antifolate	Inflammation/Immunology
Lysine-methotrexate, an analogue of Methotrexate (HY-14519), is a dihydrofolate reductase (DHFR) inhibitor .

HY-156859A

NSC309401	Bacterial	Infection
NSC309401 is an inhibitor of E. coli *DHFR* (IC₅₀: 189 nM, K_D: 14.57 nM) .

HY-156859

NSC309401 dihydrochloride	Bacterial	Inflammation/Immunology
NSC309401 is an inhibitor of E. coli *DHFR* (IC₅₀: 189 nM, K_D: 14.57 nM) .

HY-10373B

Trimetrexate isethionate CI-898 isethionate	Dihydrofolate reductase (DHFR) Antibiotic Antifolate Parasite Bacterial DNA/RNA Synthesis	Infection Cancer
Trimetrexate (CI-898) isethionate is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC₅₀ values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate isethionate can also inhibit the growth of various cancer cells. Trimetrexate isethionate can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer .

HY-156123

DHFR-IN-9	Dihydrofolate reductase (DHFR) Bacterial	Infection Cancer
DHFR-IN-9 (compound 8A) is a dihydrofolate reductase (DHFR) inhibitor that affects purine and thymidylate biosynthesis in cell proliferation and growth. DHFR-IN-9 inhibits methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 (IC₅₀=0.25 μg/mL) and has anti-infective effects in mouse models of systemic infection and thigh infection caused by it (dose: 2.5 mg /kg, 5 mg/kg; ip). DHFR-IN-9 has stronger anticancer activity than paclitaxel (Y-B0015) in a mouse model of breast cancer (dose: 2.5 mg/kg; ip; once every 3 days) .

HY-151154

EGFR/HER2/DHFR-IN-1	EGFR	Cancer
EGFR/HER2/DHFR-IN-1 is a potent anticancer agent with high selectivity against MCF-7 breast cancer cells. EGFR/HER2/DHFR-IN-1 is a multiple inhibitor of EGFR/HER2 kinase and *DHFR, with IC₅₀s of 0.153 μM, 0.108 μM, 0.291 μM, respectively. EGFR/HER2/DHFR-IN-1 arrests cell cycle at G1/S and induces cells apoptosis* .

HY-143408

OYYF-175	Bacterial	Infection
OYYF-175, an antimicrobial antifolate, is a dihydrofolate reductase (DHFR) inhibitor with an IC₅₀ of 2.36 nM for **Escherichia coli DHFR**. OYYF-175 exhibits potent broad-spectrum antibacterial activities, especially against multi-drug resistant Gram-Negative-strains .

HY-I0447A

Sodium 4-aminosalicylate dihydrate 4-Aminosalicylic acid sodium salt dihydrate	Bacterial Antibiotic	Infection
Sodium 4-aminosalicylate (Sodium para-Aminosalicylic acid) dihydrate is para-aminosalicylic acid (PAS), a dihydrofolate reductase (DHFR) inhibitor and antituberculous agent. PAS is incorporated into the folate pathway via dihydropteroate synthase (DHPS) and dihydrofolate synthase (DHFS) to generate the hydroxydihydrofolate antimetabolite, which in turn inhibits DHFR enzyme activity .

HY-151458

VEGFR-2/DHFR-IN-1	VEGFR Bacterial Dihydrofolate reductase (DHFR) Fungal	Infection Cancer
VEGFR-2/DHFR-IN-1 (compound 8b) is an inhibitor of VEGFR-2 and *DHFR* with IC₅₀s of 0.384 and 7.881 μM, respectively. VEGFR-2/DHFR-IN-1 shows good antibacterial activities against Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA and MRSA with MIC values of 16, 16, 16, 8, and 16 μg/mL, respectively. VEGFR-2/DHFR-IN-1 exhibits good cytotoxic activities against C26, HepG2, and MCF7 cancer cell lines with IC₅₀ values of 2.97-7.12 μM. VEGFR-2/DHFR-IN-1 can be used for the research of cancer .

HY-168069

DHFR-IN-20	Parasite Dihydrofolate reductase (DHFR)	Infection
DHFR-IN-20 (Compound LA1) is a Plasmodium falciparum dihydrofolate reductase (DHFR) inhibitor, with K_is of 0.16, 0.30, 6.6 nM for PfDHFR-WT, PfDHFR-QM, HsDHFR. DHFR-IN-20 has antimalarial activities (IC₅₀: 1.4 nM and 1.6 μM for P. falciparum carrying the wild-type (TM4/8.2) and the quadruple mutant (V1/S) PfDHFR enzyme .

HY-139743R

Aditoprime (Standard)	Antifolate Bacterial	Infection
Aditoprime (Standard) is the analytical standard of Aditoprime. This product is intended for research and analytical applications. Aditoprime (Aditoprim), a selective bacterial dihydrofolate reductase (DHFR) inhibitor, inhibits the transformation of dihydrofolic acid to tetrahydrofolic acid. Aditoprime inhibits E.coli and L.casei DHFR with IC₅₀ of 47 and 520 nM, respectively. Aditoprime has a broad antimicrobial spectrum, good antibacterial activity and excellent pharmacokinetics .

HY-154807

DQn-1	Bacterial	Infection
DQn-1 is a potent antifolate with activity against Mycobacterium tuberculosis (Mtb) (MIC₉₀=0.03 µM). DQn-1 directly inhibits DHFR enzyme activity, with IC₅₀s of 8.7 and 7.6 nM for Mtb and human DHFR enzyme, respectively .

HY-117791

(R)-Pralatrexate	Others	Cancer
(R)-Pralatrexate is the (R)-enantiomer of Pralatrexate (HY-10446). Pralatrexate is an antifolate and is a potent dihydrofolate reductasean (DHFR) inhibitor .

HY-107033R

Tetroxoprim (Standard)	Antifolate	Infection Inflammation/Immunology
Tetroxoprim (Standard) is the analytical standard of Tetroxoprim. This product is intended for research and analytical applications. Tetroxoprim is an antimicrobial *DHFR* inhibitor .

HY-149632

EGFR/HER2/DHFR-IN-2	EGFR Dihydrofolate reductase (DHFR)	Cancer
EGFR/HER2/DHFR-IN-2 (Compound 4b) is an inhibitor of EGFR, HER2, and *DHFR* (IC₅₀: 0.248, 0.156, 0.138 μM respectively). EGFR/HER2/DHFR-IN-2 has anticancer activities against a panel of cancer cells (IC₅₀: 9.14, 7.33, 14.18, 24.87, 20.07, 6.16 μM for Hep G2, HeLa, HEp-2, HCT 116, PC-3, MCF7 cells). EGFR/HER2/DHFR-IN-2 reduce breast cancer tumor growth .

HY-B0806

Proguanil 1 Publications Verification	Parasite Antifolate	Infection
Proguanil, an antimalarial proagent, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil is a dihydrofolate reductase (DHFR) inhibitor .

HY-B0806A

Proguanil hydrochloride 1 Publications Verification	Parasite Antifolate	Infection
Proguanil hydrochloride, an antimalarial proagent, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is a dihydrofolate reductase (DHFR) inhibitor .

HY-121207

Denopterin Pteroylglutamic acid	Antifolate Nucleoside Antimetabolite/Analog	Cancer
Denopterin is a dihydrofolate reductase (DHFR) inhibitor and an antifolate agent. Denopterin is an antimetabolite that has toxic effects on cells and can be used for cancer .

HY-149459A

Phototrexate (E)-azoMTX	Dihydrofolate reductase (DHFR)	Cancer
Phototrexate is a photoswitchable inhibitor of the human dihydrofolate reductase (DHFR). Phototrexate has antifolate and antiproliferative properties, which can be used for the research of cancer .

HY-119613

Clociguanil BRL 50216	Parasite Dihydrofolate reductase (DHFR)	Infection Cardiovascular Disease
Clociguanil (BRL 50216), a *DHFR* inhibitor (IC₅₀: 55.6 nM), is an antimalarial agent. Clociguanil has sympathomimetic and antiarrhythmic action .

Cat. No.	Product Name	Category	Target	Chemical Structure

HY-N10791

Neobritannilactone B	Zingiber officinale Roscoe Structural Classification Terpenoids Sesquiterpenes Source classification Plants Zingiberaceae	Others
Neobritannilactone B, a sesquiterpene, can be isolated from the chloroform fraction of the I. britannica. Neobritannilactone B is cytotoxic. Other extracts of I. britannica are also Dihydrofolate reductase (DHFR) inhibitors, which inhibit Shigella dysenteriae type 1 .

HY-N3764

Diosbulbin C	Structural Classification Terpenoids Source classification Diterpenoids Plants Dioscorea bulbifera Linn. Dioscoreaceae	Akt Dihydrofolate reductase (DHFR) Endogenous Metabolite
Diosbulbin C is a diterpene lactone component, which can be extracted from traditional Chinese medicine Dioscorea bulbifera L.. Diosbulbin C possesses high anticancer activity in non-small cell lung cancer (NSCLC). Diosbulbin C could induce cell cycle arrest at G0/G1 phase in NSCLC. Diosbulbin C also inhibits the proliferation of NSCLC cells, possibly by downregulating the expression/activation of AKT, *DHFR, and TYMS* .

Cat. No.	Product Name	Chemical Structure

HY-18062S

Pyrimethamine-d3
Pyrimethamine-d₃ is the deuterium labeled Pyrimethamine. Pyrimethamine is a medication used for protozoal infections; interferes with tetrahydrofolic acid synthesis from folic acid by inhibiting the enzyme dihydrofolate reductase (DHFR)[1][2].

HY-B0806AS1

Proguanil-d6 hydrochloride
Proguanil-d₆ hydrochloride is the deuterium labeled Proguanil hydrochloride (HY-B0806A). Proguanil hydrochloride, an antimalarial proagent, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is a dihydrofolate reductase (DHFR) inhibitor .

HY-B0806AS

Proguanil-d4 hydrochloride
Proguanil-d₄ (hydrochloride) is the deuterium labeled Proguanil hydrochloride. Proguanil hydrochloride, an antimalarial proagent, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is a dihydrofolate reductase (DHFR) inhibitor[1][2].

HY-B0806S1

Proguanil-d4
Proguanil-d₄ is the deuterium labeled Proguanil[1]. Proguanil, an antimalarial proagent, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil is a dihydrofolate reductase (DHFR) inhibitor[2][3].

HY-10820S

Pemetrexed-d5
Pemetrexed-d₅ is the deuterium labeled Pemetrexed[1]. Pemetrexed (LY231514) is an antifolate, the Ki values of the pentaglutamate of Pemetrexed (LY231514) are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively[2].

HY-10820AS

Pemetrexed-d5 disodium
Pemetrexed-d₅ (disodium) is the deuterium labeled Pemetrexed disodium. Pemetrexed disodium (LY231514 disodium) is an antifolate, the Kis of the pentaglutamate of Pemetrexed disodium are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively[1].

Cat. No.	Product Name		Classification

HY-10446

Pralatrexate 5+ Cited Publications		Alkynes
Pralatrexate is an antifolate and is a potent dihydrofolate reductasean (DHFR) inhibitor with a K_i of 13.4 pM. Pralatrexate is a substrate for folylpolyglutamate synthetase with improved cellular uptake and retention. Pralatrexate has antitumor activities and has the potential for relapsed/refractory T-cell lymphoma treatment . Pralatrexate is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

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DHFR inhibitor

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