250143-83-0

Upstream product

• 1041170-98-2 C₂₄H₂₃F₃N₈O₈S 
• 59-30-3 folate 
• 59-30-3 (S)-2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzamido)pentanedioic acid 
• 153445-05-7 (S)-2-(4-(((2-amino-4-hydroxypteridin-6-yl)methyl)amino)benzamido)-5-((2,5-dioxopyrrolidin-1-yl)oxy)-5-oxopentanoic acid 
• 103213-32-7 N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine 
• 1041170-98-2 N₁₀-Tfa-Pte-L-Glu-L-Cys 
• 37793-53-6 N₁₀-trifluoroacetylpteroic acid 
• 84793-07-7 Fmoc-Glu-OtBu 

Downstream Products

• 1041170-96-0 C₇₂H₇₇N₉O₂₃S₂ 

Relevant academic research and scientific papers

Radiosynthesis and evaluation of a 99mTc-folic acid radiotracer prepared using [99mTcN(PNP)]2+ metal fragment

Folate receptors (FR) are over-expressed on a wide variety of tumor cells and are a potential molecular target for radiolabeled folates. In this respect, several SPECT and PET based radiofolates have been evaluated in the past albeit with their high renal uptake posing limitation towards their clinical use. To overcome this, a new 99mTc labeled folic acid was synthesized via the use of [99mTcN(PNP)]2+ metal fragment, where the presence of the latter pharmacophore redirects in vivo clearance via the hepatobiliary pathway. In this respect, folic acid was derivatized at the γ-acid group with a cysteine BFCA (bifunctional chelating agent) and subsequently reacted with the preformed [99mTcN]2+ intermediate in presence of PNP2 (bisphosphine) ligand, to yield the final complex. While preliminary, in vivo distribution of the complex exhibited high association of activity with liver and intestines and provided support to the rationality of the present design as clearance of labeled folic acid could be effected via the hepatic route, the in vitro studies of the folic acid-cysteine conjugate carried out in KB-31 cells, did not show much promise with reduction in receptor affinity in comparison with the native folic acid. The route followed herein to prepare a folic-acid based radiotracer constitutes the first report of radiolabeling folic acid using the [99mTcN(PNP)]2+ as a radiosynthon. Modification in the structure of conjugate by linking the BFCA through a long-chain linker can be envisaged to improve the affinity of [99mTcN(PNP)]-folic acid complex towards FRs.

Ligand-decorated nanogels: Fast one-pot synthesis and cellular targeting

Nanoscale vehicles for delivery have been of interest and extensively studied for two decades. However, the encapsulation stability of hydrophobic drug molecules in delivery vehicles and selective targeting these vehicles into disease cells are potential hurdles for efficient delivery systems. Here we demonstrate a simple and fast synthetic protocol of nanogels that shows high encapsulation stabilities. These nanogels can also be modified with various targeting ligands for active targeting. We show that the targeting nanogels (T-NGs), which are prepared within 2 h by a one-pot synthesis, exhibit very narrow size distributions and have the versatility of surface modification with cysteine-modified ligands including folic acid, cyclic arginine-glycine-aspartic acid (cRGD) peptide, and cell-penetrating peptide. T-NGs hold their payloads, undergo facilitated cell internalization by receptor-mediated uptake, and release their drug content inside cells due to the reducing intracellular environment. Selective cytotoxicity to cells, which have complementary receptors, is also demonstrated.

NEW TARGETED CYTOTOXIC RATJADONE DERIVATIVES AND CONJUGATES THEREOF

The present invention is directed to novel natural product-derived ratjadone-based compounds useful as payloads (or toxins) in drug-conjugates constructs with cell target binding moieties (CTBM) and payload-linker compounds useful in connection with drug conjugates. The present invention further relates to new ratjadone compositions including the aforementioned payloads, payload-linkers and drug conjugates, and methods for using these payloads, payload-linkers and drug conjugates, to treat pathological conditions including cancer, inflammatory and infectious diseases.

Ex vivo flow cytometry method and device

The invention relates to a method for diagnosing a disease state mediated by pathogenic cells. The method comprises the steps of combining with an ex vivo patient sample a composition comprising a conjugate or complex of the general formula [in-line-formulae]Ab-X[/in-line-formulae] wherein the group Ab comprises a ligand that binds to the pathogenic cells and the group X comprises an imaging agent, and detecting the pathogenic cells that express a receptor for the ligand using flow cytometry.

Combined muta- and semisynthesis: A powerful synthetic hybrid approach to access target specific antitumor agents based on ansamitocin P3

Access of four new tumor specific folic acid/ansamitocin conjugates is reported that relies on a synthetic strategy based on the combination of mutasynthesis and semisynthesis. Two bromo-ansamitocin derivatives were prepared by mutasynthesis or by a modif

Design and synthesis of releasable folate-drug conjugates using a novel heterobifunctional disulfide-containing linker

Cellular uptake of vitamin folic acid occurs via folate-receptor mediated endocytosis. Many types of cancer cells express high levels of folate receptors as they need continuous supply of this vitamin for their proliferation. With an objective to use foli

Imaging and therapeutic method using monocytes

The invention relates to a method of treating or diagnosing a disease state mediated by monocytes. The method utilizes a composition comprising a conjugate or complex of the general formula [in-line-formulae]Ab-X [/in-line-formulae]wherein the