Delving into the Latest Updates on Aminopterin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

4-amino-4-deoxypteroylglutamate, 4-amino-PGA, 4-aminofolic acid

+ [13]

Target

DHFR

Mechanism

DHFR inhibitors(Dihydrofolate reductase inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

PsoriasisRecurrent Endometrial CancerRefractory Acute Leukemia+ [2]

Originator Organization

Genzyme Corp.

Active Organization-

Inactive Organization

Syntrix Biosystems, Inc.

Genzyme Corp.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H20N8O5

InChIKeyTVZGACDUOSZQKY-LBPRGKRZSA-N

CAS Registry54-62-6

In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, α_IIBβ₃ and α₅β₁integrins, human dihydrofolate reductase, main protease (M^pro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (-8.2 kcal/mol), α_IIBβ₃ and α₅β₁ integrins (-9.0 and -10.8 kcal/mol, respectively), human dihydrofolate reductase (-9.7 kcal/mol), M^pro of SARS-CoV-2 (-6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (-8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown.Communicated by Ramaswamy H. Sarma.

31 Aug 2024·Cureus

Dr. Sidney Farber (1903-1973): Founder of Pediatric Pathology and the Father of Modern Chemotherapy

Review

Author: Kumar Upadhyay, Amitabh ; Sinha, Neetesh ; Kumar, Abhishek ; Jena, Sanghamitra ; Prakash, Aaditya ; Sharma, Swati

Dr. Sidney Farber (Farber) was a distinguished pediatric pathologist and widely recognized pioneer of modern chemotherapy. In 1948, his influential study showed that various anti-folates, particularly 4-aminopteroylglutamic acid, also known as aminopterin, induced transient disease control in kids who had acute undifferentiated leukemia. The findings laid the basis for developing and using additional chemotherapies, individually or in combination, for treating pediatric and adult cancers. Farber also introduced actinomycin D to treat Wilms tumor in various stages. Underneath his oversight, the 'Jimmy Fund,' one of the earliest dedicated pediatric oncology centers, and the Children's Cancer Research Foundation, which subsequently evolved into the Dana-Farber Cancer Institute, was established. Farber is known as the "Founder of Pediatric Pathology" and the "Father of Modern Chemotherapy," citing his immense contributions. This article is a tribute to the great scientist Farber for his significant contributions to the scientific field and the countless individuals he has impacted.

06 Feb 2024·ACS Omega

Biocompatible, Injectable, and Self-Healing Poly(N-vinylpyrrolidone)/Carboxymethyl Cellulose Hydrogel for Drug Release

Article

Author: Lin, Xinxing ; Tang, Zuwu ; Pan, Yuwei ; Yu, Meiqiong ; Mondal, Ajoy Kanti ; Yang, Yuqing

Hydrogels have drawn intensive attention as fascinating materials for biomedicine. However, fabricating hydrogels with injectable and self-healing properties remains a challenge. Herein, we reported a biocompatible poly(N-vinylpyrrolidone)/carboxymethyl cellulose (PVP/CMC) hydrogel with excellent injectable and self-healing properties. The PVP/CMC hydrogel exhibits good biocompatible, injectable, and self-healing properties. The sol-gel transition of PVP/CMC hydrogels demonstrates an outstanding self-healing behavior, and the bisected hydrogels can self-heal within 30 s. The hydrogels have a good swelling ratio, and the swelling ratio increases with increasing amount of CMC in PVP and reaches a maximum of 2850% at a 1.0:1.5 PVP and CMC ratio. In addition, the hydrogel possesses excellent drug release capacity, and its drug release rate reaches 70%. Moreover, the release of 4-aminosalicylic acid (4-ASA) in the hydrogel can be controlled by adjusting the proportion of the hydrogel. The PVP/CMC hydrogel with excellent biocompatible, injectable, and self-healing properties has great potential for applications in drug release.

100 Deals associated with Aminopterin

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External Link

KEGG	Wiki	ATC	Drug Bank
D02527	Aminopterin	-	DB08878

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Psoriasis	Phase 2	US	Syntrix Biosystems, Inc.	01 Nov 2018
Rheumatoid Arthritis	Phase 2	UA	Syntrix Biosystems, Inc.	01 Feb 2013
Recurrent Endometrial Cancer	Phase 2	US	Genzyme Corp.	01 Jan 1998
Refractory Acute Leukemia	Phase 2	US	Genzyme Corp.	01 Jul 1997
Refractory Leukemia	Phase 2	US	Genzyme Corp.	01 Jul 1997

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03431974 (CTgov)	Phase 2	Psoriasis	19	LD-Aminopterin oral capsule (LD-Aminopterin Oral Capsule)	hktqehkqhd(zvrfhosicb) = stdrogtljy nsllagkoqe (slbhcpyxdm, tfvzyegqwf - yofphwzgsg) View more	-	14 Apr 2023
				Placebo oral capsule (Placebo Oral Capsule)	hktqehkqhd(zvrfhosicb) = pfzzyaowpn nsllagkoqe (slbhcpyxdm, bvcikmdprj - jftfwpmxlc) View more
NCT00176462 (CTgov)	Phase 2	Acute Lymphoblastic Leukemia	60	Daunomycin+Cyclophosphamide+leucovorin+Hydrocortisone+6-thioguanine+aminopterin+6-mercaptopurine+dexamethasone+Vincristine+Methotrexate+Cytarabine+L-Asparaginase (Arm 2 High Risk)	cfvrphwjwz(rxryyguvhc) = ukeltcieed lvynxlevys (hsrdhbvvtq, hrnyvqzrjm - kpodlztmwe) View more	-	09 Jun 2014
				Daunomycin+leucovorin+Hydrocortisone+6-mercaptopurine+dexamethasone+Methotrexate+Vincristine+Cytarabine+L-Asparaginase (Arm 1 Standard Risk)	vbqwfhvsyg(jobasffebi) = fwhmrijbnm brimtabgbd (dlyybwepul, ruzfrjthbk - bitparcvzl) View more