CAS 121268-17-5|Alendronate sodium
Introduction：Basic information about CAS 121268-17-5|Alendronate sodium, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Alendronate sodium | ||
|---|---|---|---|
| CAS Number | 121268-17-5 | Molecular Weight | 325.124 |
| Density | 1.857g/cm3 | Boiling Point | 616.7ºC at 760 mmHg |
| Molecular Formula | C4H18NNaO10P2 | Melting Point | 245°C |
| MSDS | ChineseUSA | Flash Point | 326.7ºC |
| Symbol | GHS07 | Signal Word | Warning |
Names
| Name | alendronate sodium trihydrate |
|---|---|
| Synonym | More Synonyms |
Alendronate sodium BiologicalActivity
| Description | Alendronate (sodium hydrate) is a farnesyl diphosphate synthase inhibitor with IC50 of 460 nM. |
|---|---|
| Related Catalog | Signaling Pathways >>Others >>OthersResearch Areas >>Cancer |
| Target | IC50: 460 nM (farnesyl diphosphate synthase) |
| In Vitro | Alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function[1]. Alendronate inhibits the isoprenoid biosynthesis pathway and interferes with protein prenylation, as a result of reduced geranylgeranyl diphosphate levels. Alendronate inhibits the incorporation of [3H]mevalonolactone into proteins of 18-25 kDa and into nonsaponifiable lipids, including sterols in osteoclasts[2]. Alendronate causes a dose-dependent inhibition of [3H]MVA incorporation into sterols and a concomitant increase in incorporation of radiolabel into IPP and DMAPP[3]. |
| In Vivo | Alendronate causes erosions in the rabbit stomach, but not antral ulceration in rats. Alendronate increases the incidence and size of indomethacin-induced antral ulcers. Alendronate also enhances indomethacin-induced gastricdamage in the rat, and delays gastric ulcer healing[4]. Alendronate (0.04-0.1 mg/kg twice weekly or 0.1 mg/kg weekly) partially blocks the establishment of bone metastases by human PC-3 ML cells and results in tumor formation in the peritoneum and other soft tissues. Alendronate pretreatment of mice (0.1 mg/kg twice weekly or weekly) and dosing along with taxol (10-50 mg/kg/day, twice weekly, or weekly) blocks the growth of PC-3 ML tumors in the bone marrow and soft tissues in a statistically significant manner and improves survival rates significantly by 4-5 weeks[5]. |
| Kinase Assay | Rat liver cytosol is prepared from a separate piece of liver from rat. Assays are carried out in a total volume of 0.1 mL containing 10 mg of cytosolic protein, and components according to Rilling. All reaction components (except IPP) are mixed and kept on ice for 15 min. Reactions are initiated by the addition of [14C]IPP and incubation at 37°C. Reactions are stopped after 5 min by addition of 0.4 mL MeOH/HCl (4/1, by vol.) and the samples are incubated a further 15 min to hydrolyze the allylic pyrophosphates to petroleum ether-extractable products. Following addition of 0.5 mL water and 1 mL petroleum ether, 50% of the upper (petroleum ether-extractable) phase is taken for liquid scintillation analysis. Preliminary experiments indicated that the reaction is linear with time and protein under these conditions, and no more than 10% of the substrate is consumed. |
| References | [1]. Fisher JE, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):133-8. [2]. Bergstrom JD, et al. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41. [3]. Keller RK, et al. Mechanism of aminobisphosphonate action: characterization of alendronate inhibition of the isoprenoid pathway. Biochem Biophys Res Commun. 1999 Dec 20;266(2):560-3. [4]. Elliott SN, et al. Alendronate induces gastric injury and delays ulcer healing in rodents. Life Sci. 1998;62(1):77-91. [5]. Stearns ME, et al. Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice. Invasion Metastasis. 1996;16(3):116-31. |
Chemical & Physical Properties
| Density | 1.857g/cm3 |
|---|---|
| Boiling Point | 616.7ºC at 760 mmHg |
| Melting Point | 245°C |
| Molecular Formula | C4H18NNaO10P2 |
| Molecular Weight | 325.124 |
| Flash Point | 326.7ºC |
| Exact Mass | 325.030365 |
| PSA | 211.45000 |
| Storage condition | −20°C |
| Stability | Store in freezer |
| Water Solubility | water, double-distilled: 10 mg/mL |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Human - woman
- DOSE/DURATION :
- 700 ug/kg/7D-I
- TOXIC EFFECTS :
- Gastrointestinal - changes in structure or function of esophagus Gastrointestinal - other changes
- REFERENCE :
- AJGAAR American Journal of Gastroenterology. (American College of Gastroenterology, Inc., 428 E. Preston St., Baltimore, MD 21202) V.21- 1954- Volume(issue)/page/year: 90,1889,1995
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 30 mg/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3229,1994
- TYPE OF TEST :
- LDLo - Lowest published lethal dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 10 mg/kg
- TOXIC EFFECTS :
- Behavioral - ataxia Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3229,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 9100 ug/kg/13W-I
- TOXIC EFFECTS :
- Blood - pigmented or nucleated red blood cells Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3244,1994 ** REPRODUCTIVE DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 510 mg/kg
- SEX/DURATION :
- female 14 day(s) pre-mating - 20 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Maternal Effects - parturition Reproductive - Maternal Effects - other effects Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)
- REFERENCE :
- TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 121,217,1993
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 42 mg/kg
- SEX/DURATION :
- male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Maternal Effects - other effects Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3319,1994
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 27500 ug/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical Reproductive - Effects on Newborn - delayed effects
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3339,1994
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 26 mg/kg
- SEX/DURATION :
- female 17-21 day(s) after conception lactating female 21 day(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical Reproductive - Effects on Newborn - delayed effects
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3373,1994
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- DOSE :
- 650 ug/kg
- SEX/DURATION :
- female 6-18 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Maternal Effects - other effects
- REFERENCE :
- KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 28,3363,1994
Safety Information
| Symbol | GHS07 |
|---|---|
| Signal Word | Warning |
| Hazard Statements | H302 |
| Precautionary Statements | P301 + P312 + P330 |
| Personal Protective Equipment | dust mask type N95 (US);Eyeshields;Gloves |
| Hazard Codes | Xn,Xi |
| Risk Phrases | R22:Harmful if swallowed. R36/37/38:Irritating to eyes, respiratory system and skin . |
| Safety Phrases | S26:In case of contact with eyes, rinse immediately with plenty of water and seek medical advice . S36:Wear suitable protective clothing . |
| RIDADR | NONH for all modes of transport |
| WGK Germany | 3 |
| RTECS | SZ6523500 |
| HS Code | 29310095 |
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Synonyms
| Alendronate sodium |
| (4-Amino-1-hydroxy-1-phosphonobutyl)phosphonic Acid Monosodium Salt Trihydrate |
| 4-amino-1-hydroxy-1-phosphonobutyl phosphonic acid,monosodium,Alendronate sodium trihydrate |
| Phosphonic acid, (4-amino-1-hydroxybutylidene)bis-, sodium salt, hydrate (1:1:3) |
| Alendronate sodium trihydrate |
| Sodium Alendronate Trihydrate |
| hydrogène (4-amino-1-hydroxy-1-phosphonobutyl)phosphonate de sodium trihydrate |
| alendronate sodium hydrate |
| Monosodium (4-Amino-1-hydroxy-1-phosphonobutyl)phosphonate Trihydrate |
| Alendronate monosodium trihydrate |
| MFCD01748233 |
| Alendronic acid monosodium salt trihydrate |
| Sodium hydrogen (4-amino-1-hydroxy-1-phosphonobutyl)phosphonate hydrate (1:1:3) |
| onclast |
| Adronat |
| Natriumhydrogen-(4-amino-1-hydroxy-1-phosphonobutyl)phosphonattrihydrat |
| 4-amino-1-hydroxy-1-phosphonobutyl phosphonic acid,monosodium MK-217 |
| Dronal |
| Sodium alendronate |
| Alendronate (sodium hydrate) |
