prodrug

Etoposide (VP-16-213) is a topoisomerase II inhibitor that inhibits DNA synthesis by forming a complex with topoisomerase II and DNA (IC50=60.3 μM). Etoposide has antitumor activity and induces apoptosis and autophagy.

Clindamycin Phosphate is the phosphate salt form of clindamycin, a semi-synthetic, chlorinated broad-spectrum antibiotic produced by chemical modification of lincomycin. Clindamycin phosphate (Clindamycin 2-dihydrogen phosphate) is used in topical preparations.

Adefovir dipivoxil (GS 0840) is a dipivoxil formulation of adefovir, a nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV).

Myristyl nicotinate (Tetradecyl nicotinate) is an ester prodrug being developed for delivering nicotinic acid (NIC) into the skin to prevent actinic keratosis and its progression to skin cancer.

Isavuconazole (RO-0094815)(BAL-4815; RO-0094815) is the active component of the new azole antifungal agent BAL8557 with MIC(50)s/MIC(90)s ranged from 0.002/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata.

Dabigatran Etexilate Mesylate (BIBR 1048MS) is the orally active prodrug of dabigatran. Dabigatran is a reversible and selective, direct thrombin inhibitor (DTI, Ki: 4.5 nM).

Testosterone acetate (NSC-523836) is a hormone with in vitro antitumor activity.

Valecobulin hydrochloride (CKD-516 hydrochloride) is the valine prodrug and vasoblocker of S516. Valecobulin hydrochloride (CKD-516 hydrochloride) has a potent inhibitory effect on β-tubulin polymerization and has significant anti-tumor activity against solid tumors in mice and humans.

Dexamethasone palmitate (DXP), a lipophilic prodrug of Dexamethasone, shows a 47-fold lower affinity for the glucocorticoid receptor than Dexamethasone. Dexamethasone palmitate is a glucocorticoid receptor agonist and an anti-inflammatory agent.

Tributyrin (Glyceryl tributyrate), a neutral short-chain fatty acid triglyceride, is a stable and rapidly absorbed prodrug of Butyric Acid. It diffuses through biological membranes and is metabolized by intracellular lipases, releasing effective butyrate directly into cells in vivo, exhibiting potent proapoptotic, antiproliferative, and differentiation-inducing effects.

Etilevodopa hydrochloride (L-DOPA ethyl ester) is a prodrug of levodopa. It also has greater gastric solubility and significant brain penetration.

Isavuconazonium sulfate is hydrolyzed by plasma esterases to yield the active moiety isavuconazole. Isavuconazole binds to and inhibits the fungal cytochrome P450 family enzyme lanosterol 14-alpha-demethylase (CYP51), which catalyzes the demethylation of

Ceftobiprole medocaril (BAL5788), the parenteral prodrug of Ceftobiprole, is a broad-spectrum cephalosporin effective against Methicillin-resistant Staphylococcus aureus (MRSA).

Ceftaroline fosamil (TAK-599) is a cephalosporin, with activity against Gram-positive pathogens.

2',3',5'-triacetyl-5-Azacytidine (Nsc291930) is a prodrug form of 5-azacytidine that may be rapidly absorbed orally.

Beraprost sodium is a stable and orally active prodrug of PGI2.

Melflufen (Melphalan flufenamide), a dipeptide proagent of Melphalan, is an alkylating agent. Melflufen exhibits significant antitumor activity against multiple myeloma (MM) cells and has been shown to inhibit angiogenesis. Melflufen induces irreversible DNA damage and cytotoxicity in MM cells, thereby contributing to its antitumor efficacy. At equivalent molar concentrations, both the salt and free forms of Melflufen exhibit comparable biological activity. However, the salt form, Melflufen hydrochloride, typically demonstrates enhanced water solubility and stability, which may contribute to its increased therapeutic potential.

Evofosfamide (TH-302) is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) conjugated with 2-nitroimidazole, possessing potential antineoplastic activity. Under hypoxic conditions, typical of hypoxic tumors, the 2-nitroimidazole moiety is reduced, releasing the DNA-alkylating Br-IPM moiety, which induces intra- and inter-strand DNA crosslinks that inhibit DNA replication and cell division, potentially causing apoptosis in tumor cells. The inactive form of the prodrug remains stable under normoxic conditions, which may reduce systemic toxicity.

PRI-724 is a second-generation, selective small molecule inhibitor of the β-catenin/CBP interaction.

Tubulin Polymerization-IN-1 prodrug (Compound 2b) is a microtubule polymerization inhibitor prodrug mediated by Pd. Developed from colchicine-binding site inhibitors (CBSIs), it aims to reduce toxicity and enhance targeted release. Compared to the parent compound, its cytotoxicity is decreased by 68.3 times, but can be in situ restored in the presence of Pd resin. Mechanistic studies show it retains the same antitumor activity as CBSIs. In vivo tests demonstrate that, once activated by Pd resin, it significantly suppresses tumor growth (63.2% inhibition rate). Tubulin Polymerization-IN-1 prodrug is a promising candidate for cancer research.

TrxR1 prodrug-1 (compound 5u) is a potent inhibitor of TrxR1, demonstrating significant antitumor activity in nude mice and NSCLC organoids.

Itaconic acid prodrug-1 (Compound P2) is an orally active prodrug of Itaconic acid that efficiently delivers Itaconic acid to skin tissues upon oral administration. It exhibits immunomodulatory effects, significantly inhibiting Poly(I:C)/IFNγ-induced inflammatory cytokines in human epidermal keratinocytes. Itaconic acid prodrug-1 is useful for research into alopecia areata and other inflammatory skin conditions.

TP prodrug (compound 15) is an effective and orally active anti-SARS-CoV-2 agent. The 13-TP prodrug exhibits cytotoxic properties and can reduce the expression of the SARS-CoV-2 N protein. Additionally, the 13-TP prodrug demonstrates antiviral activity.

IDOi-Pt(IV) prodrug-1 (Compound 10) is an IDOi-Pt(IV) prodrug that suppresses IDO expression. It induces apoptosis, reduces mitochondrial membrane potential, and inhibits tumor cell migration and invasion. Additionally, IDOi-Pt(IV) prodrug-1 triggers reactive oxygen species-mediated endoplasmic reticulum stress and the secretion of damage-associated molecular patterns (DAMPs), leading to immunogenic cell death (ICD). Compared to cisplatin, IDOi-Pt(IV) prodrug-1 exhibits relatively high efficiency and low toxicity in its antitumor activity.