595-33-5 Usage
Description
Megestrol acetate, also known as Megace, is a synthetic derivative of the naturally occurring female sex hormone progesterone. It is a progestin with potential anti-estrogenic and antineoplastic activity, primarily used for the palliative management of recurrent, inoperable, or metastatic endometrial or breast carcinoma. Megestrol acetate is also an appetite stimulant and has been indicated for appetite enhancement in patients with AIDS.
Used in Oncology:
Megestrol acetate is used as an antineoplastic agent for the treatment of carcinoma of the breast or endorometrium. It is particularly effective in managing recurrent, inoperable, or metastatic cases of endometrial or breast cancer.
Used in Appetite Stimulation:
Megestrol acetate is used as an appetite stimulant for patients with cancer and acquired immunodeficiency syndrome (AIDS). It is useful in cases where profound anorexia is the main manifestation of cachexia and if the expected survival is weeks to months. It has been shown to significantly increase appetite, although it does not affect survival.
Used in Cachexia Management:
Megestrol acetate is used to manage cachexia in cancer patients, as it has been shown to produce weight gain in various cachectic cancer patients. The improvement in appetite and body weight gain may be due to the significant reduction in serum levels of IL-1a and b, IL-2, IL-6, and TNF-o observed in cancer patients treated with megestrol acetate. It has also been postulated that the effect is, at least in part, mediated by NPY, a potent central appetite stimulant.
Used in Contraception:
Megestrol acetate has a role as a contraceptive drug, although it is not commonly used for this purpose due to its other therapeutic applications.
Used in Pharmaceutical Industry:
Megestrol acetate is used as a progestin in the pharmaceutical industry for the development of drugs targeting cancer and appetite stimulation in patients with specific conditions.
Brand Names:
Megace (Bristol-Myers Squibb); Megace (Par).
Originator
Megestat,Bristol,W. Germany,1964
Manufacturing Process
The following preparation is given in US Patent 3,356,573. 17α-Acetoxy-3βhydroxy-6-methylpregn-5-ene-20-one (1 g), aluminum tert-butoxide (1 g) and p-benzoquinone (6 g) were dissolved in dry benzene (100 ml) and the mixture was heated under reflux for 30 minutes. The reaction mixture was cooled and washed with potassium hydroxide solution until the benzene layer was colorless. The benzene was washed with water, dried and evaporated to dryness under reduced pressure. The residue crystallized from aqueous methanol to give 17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione, needles, MP 214° to 216°C.
Therapeutic Function
Cancer chemotherapy
Clinical Use
Progestin activity is further enhanced when a double bond is introduced between positions 6 and 7, as is found in megestrol
acetate. Megestrol is used primarily in the treatment of breast and endometrial carcinomas and in postmenopausal
women with advanced hormone-dependent carcinoma.
Safety Profile
Suspected carcinogen
with experimental carcinogenic and
teratogenic data. Poison by intravenous
route. Human reproductive effects bp
ingestion and implant routes: effects on
ovaries and fallopian tubes, menstrual cycle
changes, and female fertility index changes.
Mutation data reported. Experimental
reproductive effects. When heated to
decomposition it emits acrid smoke and
irritating fumes. An FDA proprietary drug
used to treat endometriosis and breast
cancer. A steroid.
Veterinary Drugs and Treatments
Megestrol acetate (Ovaban?—Schering) is approved by FDA for use
in dogs only for the postponement of estrus and the alleviation of
false pregnancy. In male dogs, it has been used for benign prostatic
hypertrophy. It is used clinically for many dermatologic and behavior-
related conditions, primarily in the cat. See the Dosage section
for specific indications and dosages for both dogs and cats.
Megestrol acetate is indicated in humans for the palliative treatment
of advanced carcinoma of the breast or endometrium.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: metabolism of progestogens
accelerated by griseofulvin and rifamycins.
Anticoagulants: progestogens antagonise
anticoagulant effect of phenindione; may enhance or
reduce anticoagulant effect of coumarins.
Antiepileptics: metabolism accelerated by
carbamazepine, eslicarbazepine, fosphenytoin,
oxcarbazepine, phenobarbital, phenytoin, primidone,
rufinamide and topiramate; concentration of
lamotrigine reduced; concentration reduced by high
dose perampanel.
Antivirals: metabolism accelerated by nevirapine.
Ciclosporin: progestogens inhibit metabolism of
ciclosporin (increased plasma concentration).
Dopaminergics: concentration of selegiline increased
- avoid.
Metabolism
Less than 10% of an oral dose undergoes metabolism. Several major
metabolites appear in the urine (e.g., 2-hydroxy and 6-hydroxymethyl megestrol and their glucuronide conjugates).
references
[1] zhang k1, chow pk. the effect of megestrol acetate on growth of hepg2 cells in vitro and in vivo. clin cancer res. 2004 aug 1; 10(15):5226-32.
Check Digit Verification of cas no
The CAS Registry Mumber 595-33-5 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,9 and 5 respectively; the second part has 2 digits, 3 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 595-33:
(5*5)+(4*9)+(3*5)+(2*3)+(1*3)=85
85 % 10 = 5
So 595-33-5 is a valid CAS Registry Number.
InChI:InChI=1/C23H30O4/c1-14(24)23(27-15(2)25)12-9-20-18-6-5-16-13-17(26)7-10-21(16,3)19(18)8-11-22(20,23)4/h5-6,13,18-20H,7-12H2,1-4H3/t18-,19+,20+,21+,22+,23+/m1/s1
595-33-5Relevant articles and documents
The preparation method of the megestrol (by machine translation)
-
Paragraph 0009; 0012; 0014; 0016, (2018/01/13)
Megestrol preparation method, in order to 6 - keto - 17 a - acetoxy progesterone as raw material, the raw material in the organic solvent, in the original carboxylic acid triethyl ester existence under, with the glycol alkyd catalytic reaction double-[...]; then double [...] in the organic solvent, deprotecting reagent Grignard reaction, after the reaction in under the action of the strong acid, standard hydrolysis, at the same time deprotected, dehydration, by a two-step reaction to synthesize a megestrol crude; crude to decolorize with active carbon crystallization to, be a megestrol product, HPLC content 99.0 - 99.5%, melting point 213 - 220 °C, the weight of the two-step synthesis of the total yield of 80 - 85%. The invention relative to the traditional method, short synthetic route, the process operation is simple, production economy and environmental protection, the total synthesis than the traditional method to improve the yield of 30% or more, the production cost is reduced 30 - 35%; used in the process of recovering the solvent can be recycled, not only economic, environmental protection, and is favorable for industrial production. (by machine translation)
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
Process for the preparation of 6-methyl-Δ4,6 -3-keto steroids
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, (2008/06/13)
A process for preparing 6-methyl-Δ4,6 -3-keto steroids of the formula STR1 comprises reacting a corresponding Δ4 -3-keto steroid with methoxymethyl acetate (CH3 --O--CH2 --OAc) in an inert solvent at temperatures above room temperature in the presence of an alkali metal acetate.
