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Plicamycin | CAS No: 18378-89-7 | GMP-certified suppliers
A medication that treats testicular cancer and manages hypercalcemia and hypercalciuria related to advanced cancers, providing antineoplastic and calcium-regulating effects.
Therapeutic categories
AnthracyclinesAntibiotics, AntineoplasticAntineoplastic AgentsAntineoplastic and Immunomodulating AgentsCalcium-Regulating Hormones and AgentsCarbohydrates
Generic name
Plicamycin
Molecule type
small molecule
CAS number
18378-89-7
DrugBank ID
DB06810
Approval status
Approved drug, Investigational drug, Withdrawn drug
ATC code
L01DC02
Primary indications
- For the treatment of testicular cancer, as well as hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer
Product Snapshot
- Plicamycin is available as an injectable small molecule formulation
- It is primarily used for oncology indications, including testicular cancer, and for managing hypercalcemia and hypercalciuria related to advanced cancers
- The compound holds a variable regulatory status, with approvals in certain markets alongside periods of investigational use and withdrawal
Clinical Overview
Plicamycin (CAS Number 18378-89-7) is an antineoplastic antibiotic originally produced by the bacterium Streptomyces plicatus. It has been employed clinically in the treatment of testicular cancer, as well as in managing hypercalcemia and hypercalciuria secondary to various advanced malignancies. Additionally, plicamycin has been used in the management of Paget’s disease of bone. Despite these applications, its manufacture was discontinued by the original producer around the year 2000.
Pharmacologically, plicamycin belongs to the class of oligosaccharides, which are carbohydrates composed of three to ten monosaccharide units linked via glycosidic bonds. It exhibits potent cytotoxic activity, demonstrated by lethality to Hela cells at concentrations as low as 0.5 micrograms per milliliter within 48 hours in vitro. In vivo, plicamycin has shown significant antitumor activity against experimental leukemia in murine models when administered intraperitoneally.
The mechanism of action of plicamycin involves the inhibition of cellular and enzymatic RNA synthesis through binding and complexation with DNA. This interaction disrupts nucleic acid synthesis and subsequently impairs protein synthesis, contributing to its cytotoxicity. In its role as a calcium-regulating agent, plicamycin lowers serum calcium levels, potentially by inhibiting parathyroid hormone effects on osteoclasts or antagonizing the hypercalcemic action of pharmacologic doses of vitamin D.
Key ADME parameters are not extensively documented in the public domain due to limited contemporary clinical use. However, the compound’s toxicity profile includes notable risks of myelosuppression, hepatotoxicity, and bleeding tendencies, which require careful monitoring during use.
Plicamycin has been classified under various categories including anthracyclines, antineoplastic agents, and nucleic acid synthesis inhibitors. It is not currently marketed, and its usage today is largely limited to research settings or historical reference.
For API procurement, sourcing plicamycin presents challenges due to its discontinued commercial production. Quality assurance for any available material must prioritize rigorous identity, purity, and potency testing compliant with pharmacopeial standards to ensure suitability for pharmaceutical development or research purposes.
Pharmacologically, plicamycin belongs to the class of oligosaccharides, which are carbohydrates composed of three to ten monosaccharide units linked via glycosidic bonds. It exhibits potent cytotoxic activity, demonstrated by lethality to Hela cells at concentrations as low as 0.5 micrograms per milliliter within 48 hours in vitro. In vivo, plicamycin has shown significant antitumor activity against experimental leukemia in murine models when administered intraperitoneally.
The mechanism of action of plicamycin involves the inhibition of cellular and enzymatic RNA synthesis through binding and complexation with DNA. This interaction disrupts nucleic acid synthesis and subsequently impairs protein synthesis, contributing to its cytotoxicity. In its role as a calcium-regulating agent, plicamycin lowers serum calcium levels, potentially by inhibiting parathyroid hormone effects on osteoclasts or antagonizing the hypercalcemic action of pharmacologic doses of vitamin D.
Key ADME parameters are not extensively documented in the public domain due to limited contemporary clinical use. However, the compound’s toxicity profile includes notable risks of myelosuppression, hepatotoxicity, and bleeding tendencies, which require careful monitoring during use.
Plicamycin has been classified under various categories including anthracyclines, antineoplastic agents, and nucleic acid synthesis inhibitors. It is not currently marketed, and its usage today is largely limited to research settings or historical reference.
For API procurement, sourcing plicamycin presents challenges due to its discontinued commercial production. Quality assurance for any available material must prioritize rigorous identity, purity, and potency testing compliant with pharmacopeial standards to ensure suitability for pharmaceutical development or research purposes.
Identification & chemistry
| Generic name | Plicamycin |
|---|---|
| Molecule type | Small molecule |
| CAS | 18378-89-7 |
| UNII | NIJ123W41V |
| DrugBank ID | DB06810 |
Pharmacology
| Summary | Plicamycin exerts its therapeutic effects primarily through binding to DNA, thereby inhibiting RNA synthesis at the cellular and enzymatic levels. It also modulates calcium metabolism by interfering with parathyroid hormone actions on osteoclasts and counteracting vitamin D–induced hypercalcemia. The compound demonstrates cytotoxic activity against tumor cells and impacts calcium-related abnormalities in advanced cancers. |
|---|---|
| Mechanism of action | Plicamycin is presumed to inhibit cellular and enzymic RNA synthesis by forming a complex with DNA. Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D. |
| Pharmacodynamics | Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally. |
Targets
| Target | Organism | Actions |
|---|---|---|
| DNA | Humans | antagonist |
ADME / PK
| Protein binding | There is no evidence of protein binding, nor is there any evidence of metabolism of the carbohydrate moiety of the drug to carbon dioxide and water with loss through respiration. |
|---|---|
| Route of elimination | Radioautography studies with 3H-labeled plicamycin in mice show that the greatest concentrations of the isotope are in the Kupffer cells of the liver and cells of the renal tubules. Plicamycin is rapidly cleared from the blood within the first 2 hours and excretion is also rapid. 67% percent of measured excretion occurs within 4 hours, 75% within 8 hours, and 90% is recovered in the first 24 hours after injection. |
Formulation & handling
- Plicamycin is a small molecule oligosaccharide suitable primarily for non-oral administration due to its molecular complexity.
- Moderate water solubility and LogP indicate careful formulation design is needed to achieve adequate bioavailability.
- Stability considerations include protection from hydrolysis and monitoring during storage due to its oligosaccharide glycosidic bonds.
Regulatory status
Safety
| Toxicity | The most important form of toxicity associated with the use of plicamycin consists of a dose-related bleeding syndrome which usually begins with an episode of epistaxis. Plicamycin crosses the blood-brain barrier; the concentration found in brain tissue is low but it persists longer than in other tissues. |
|---|
High Level Warnings:
- Plicamycin exhibits dose-related hemorrhagic toxicity, frequently presenting initially as epistaxis
- The compound crosses the blood-brain barrier, with prolonged persistence in brain tissue despite low concentrations
- Careful monitoring of bleeding parameters is advised during handling due to the risk of systemic bleeding effects
Mithramycin API manufacturers & distributors
Compare qualified Mithramycin API suppliers worldwide. We currently have 1 companies offering Mithramycin API, with manufacturing taking place in 1 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Changzhou Comwin Fine Che... | Producer | China | China | BSE/TSE, CoA, EDMF/ASMF, GMP, USDMF | 235 products |
When sending a request, specify which Mithramycin API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Mithramycin API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
