197151-85-2

Upstream product

• 59-30-3 folic acid 
• 1499-55-4 L-glutamic acid 5-methyl ester 
• 107-15-3 ethylenediamine 
• 53464-60-1 L-methyl folate (γ) 
• 910661-24-4 (S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate 
• 910661-25-5 (S)-tert-butyl 2-amino-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate 
• 84793-07-7 Fmoc-Glu-OtBu 
• 153445-05-7 folic acid, N-hydroxysuccinimide ester 
• 153445-05-7 N-hydroxysuccinimide folate 
• 1017018-99-3 C₂₆H₃₃N₉O₇ 
• 197151-79-4 pteroyl azide 
• 197151-68-1 pteroyl hydrazide 
• 59-30-3 (S)-2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzamido)pentanedioic acid 
• 1049627-30-6 C₃₀H₄₁N₉O₇ 

Downstream Products

• 1608495-97-1 C₃₉H₄₄N₁₂O₇ 
• 1579248-68-2 folate-EDA-EDTA-Cys-OH 
• 1579248-67-1 folate-EDA-EDTA-Cys(Trt)-OH 

Relevant academic research and scientific papers

Development of 99mTc-labeled trivalent isonitrile radiotracer for folate receptor imaging

Folate receptors (FR) are frequently overexpressed in a wide variety of human cancers. The aim of this study was to develop a trivalent 99mTc(CO)3-labeled folate radiotracer containing isonitrile (CN-R) as the coordinating ligand for

Redirection of genetically engineered CAR-T cells using bifunctional small molecules

Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) provide a potent antitumor response and have become a promising treatment option for cancer. However, despite their efficacy, CAR-T cells are associated with significant safety challenges related to the inability to control their activation and expansion and terminate their response. Herein, we demonstrate that a bifunctional small molecule switch consisting of folate conjugated to fluorescein isothiocyanate (folate-FITC) can redirect and regulate FITC-specific CAR-T cell activity toward folate receptor (FR)-overexpressing tumor cells. This system was shown to be highly cytotoxic to FR-positive cells with no activity against FR-negative cells, demonstrating the specificity of redirection by folate-FITC. Anti-FITC-CAR-T cell activation and proliferation was strictly dependent on the presence of both folate-FITC and FR-positive cells and was dose titratable with folate-FITC switch. This novel treatment paradigm may ultimately lead to increased safety for CAR-T cell immunotherapy.

Self-assembled targeted folate-conjugated eight-arm-polyethylene glycol-betulinic acid nanoparticles for co-delivery of anticancer drugs

In this study, a targeted nanoparticle platform for co-delivery of anticancer drugs based on folate-conjugated eight-arm-polyethylene glycol-betulinic acid (F-8arm-PEG-BA) was first presented. F-8arm-PEG-BA was synthesized by introducing target molecules

Preparation and evaluation of novel folate isonitrile99mtc complexes as potential tumor imaging agents to target folate receptors

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purifica-tion, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indi-cated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had spe-cific tumor uptake. Compared with [99mTc]Tc-CN5FA, the tumor/muscle ratios of [99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99m Tc complexes have potential as tumor imaging agents to target folate receptors.

Folic acid conjugates of a bleomycin mimic for selective targeting of folate receptor positive cancer cells

A major challenge in the application of cytotoxic anti-cancer drugs is their general lack of selectivity, which often leads to systematic toxicity due to their inability to discriminate between malignant and healthy cells. A particularly promising target for selective targeting are the folate receptors (FR) that are often over-expressed on cancer cells. Here, we report on a conjugate of the pentadentate nitrogen ligand N4Py to folic acid, via a cleavable disulphide linker, which shows selective cytotoxicity against folate receptor expressing cancer cells.

A folate-conjugated platinum porphyrin complex as a new cancer-targeting photosensitizer for photodynamic therapy

A new folate-conjugated platinum porphyrin complex (Por 4) was synthesized and characterized. The singlet oxygen production of the conjugates was evaluated through a 1,3-diphenylisobenzofuran method. The targeting ability and subcellular localization of P

Synthesis of a functionalized dipeptide for targeted delivery and pH-sensitive release of chemotherapeutics

Targeted delivery of chemotherapeutics to tumor cells is one of the biggest challenges in cancer treatment. Herein, we synthesized smart dipeptide nanoparticles for cancer-specific targeting and intracellular pH-sensitive release of chemotherapeutics. Diphenylalanine peptide was synthesized and further developed as nanoparticles (NPs), which were functionalized with folic acid utilizing the carbodiimide reaction. Doxorubicin (Dox) was loaded to self-assembled non-functionalized (FF-Dox) and folate functionalized peptides NPs (FA-FF-Dox). Moreover, the experiments revealed the pH-sensitive release of Dox for both FA-FF-Dox and FF-Dox due to the protonation of the Schiff base and the amines present in the peptides at low pH, enhancing intracellular release subsequent to receptor-mediated endocytosis. Further, biodistribution and the pharmacokinetics study revealed enhanced targeting efficiency of FA-FF-Dox with high accumulation in tumor cells.

Towards potent but less toxic nanopharmaceuticals-lipoic acid bioconjugates of ultrasmall gold nanoparticles with an anticancer drug and addressing unit

Modification of ultrasmall gold nanoparticles (AuNPs) with the lipoic acid derivative of folic acid was found to enhance their accumulation in the cancer cell, as compared to AuNPs without addressing units. The application of lipoic acid enabled the control of the gold nanoparticle functionalities leading to enhanced solubility and allowing for attachment of both the folic acid and the cytotoxic drug, doxorubicin. More robust attachment of doxorubicin to the nanoparticle through the amide bond resulted in toxicity comparable with that of the drug alone, opening a new perspective for designing more potent, but less toxic nanopharmaceuticals. The increased uptake was accompanied by pronounced nuclear accumulation and observable cytotoxicity. Doxorubicin binding via covalent amide bonds enhanced stability of the whole drug vehicle and provided much better control over doxorubicin release in the cell environment, as compared to physical adsorption or pH sensitive bonding commonly used for anthracycline carriers. Confocal microscopy revealed that the bond was stable in the cytoplasm for 22 h. The ability to slow down the rate of drug release may be crucial for the application in sustained anticancer drug delivery. Biological analyses performed using MTT assay and confocal microscopy confirmed that the ultrasmall AuNPs with the lipoic acid derivative of folic acid exhibit relatively low cytotoxicity, however when loaded with a chemotherapeutic, they cause a significant reduction in the cell viability.

DRUG FORMULATION BASED ON PARTICULATES COMPRISING POLYSACCHARIDE-VITAMIN CONJUGATE

The present disclosure provides formulations for pharmacologically active reagents, including formulations based on particulates formed from a biodegradable polymer (e.g., a polysaccharide such as dextran) linked to a vitamin or related agent (e.g., folic