Cladribine CAS 4291-63-8
Introduction：Basic information about Cladribine CAS 4291-63-8, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Cladribine Basic informationDescription References
| Product Name: | Cladribine |
| Synonyms: | 2-CHLORO-2'-DEOXYADENOSINE;2CDA;2-CL-DADO;CDA;CLADRIBINE;CLADRIBINE CDA;LABOTEST-BB LT01147851;2-Chloro-6-amino-9-(2-deoxy-b-D-erythro-pentofuranosyl)purine |
| CAS: | 4291-63-8 |
| MF: | C10H12ClN5O3 |
| MW: | 285.69 |
| EINECS: | 636-978-6 |
| Product Categories: | Inhibitors;API;Anti-cancer&immunity;Bases & Related Reagents;Nucleotides;Pharmaceuticals |
| Mol File: | 4291-63-8.mol |
Cladribine Chemical Properties
| Melting point | 181-185 °C(lit.) |
| alpha | D25 -18.8° (c = 1 in DMF) |
| Boiling point | 547.6±60.0 °C(Predicted) |
| density | 2.03±0.1 g/cm3(Predicted) |
| storage temp. | -20°C |
| solubility | Slightly soluble in water, soluble in dimethyl sulfoxide, slightly soluble in methanol, practically insoluble in acetonitrile. It shows polymorphism (5.9). |
| pka | 13.75±0.60(Predicted) |
| form | White solid |
| color | White to Pale Yellow |
| λmax | 265nm(EtOH aq.)(lit.) |
| Merck | 14,2337 |
| Stability: | Store in Freezer |
| Major Application | pharmaceutical (small molecule) |
| InChI | InChI=1S/C10H12ClN5O3/c11-10-14-8(12)7-9(15-10)16(3-13-7)6-1-4(18)5(2-17)19-6/h3-6,17-18H,1-2H2,(H2,12,14,15)/t4-,5+,6+/m0/s1 |
| InChIKey | PTOAARAWEBMLNO-HSUXUTPPSA-N |
| SMILES | OC[C@H]1O[C@@H](N2C3C(=C(N=C(Cl)N=3)N)N=C2)C[C@@H]1O |
| CAS DataBase Reference | 4291-63-8(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 36/37/38-23/24/25 |
| Safety Statements | 26-37/39-45-36-22 |
| RIDADR | UN 2811 6.1 / PGIII |
| WGK Germany | 3 |
| RTECS | AU7357560 |
| HS Code | 29349990 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral Muta. 2 Repr. 2 STOT RE 1 |
| Hazardous Substances Data | 4291-63-8(Hazardous Substances Data) |
| Toxicity | LD50 intraperitoneal in mouse: 150mg/kg |
| Description | Cladribine (2-chloro-2′-deoxyadenosine) is an adenosine deaminase-resistant analogue of deoxyadenosine. The drug has a broad range of in vitro activity against both lymphoid and myeloid neoplasms [mean IC50values (drug concentration required to inhibit cell growth by 50% of control): 20 to 87 nmol/L]. But it possesses little activity against multiple myeloma specimens and many solid tumor cell lines. Monocytes are highly sensitive to cladribine in vitro. Cladribine demonstrates activity against both dividing and nondividing cells and this activity distinguishes it from many other agents. It has activity in murine models of leukaemia. Cladribine is used to treat chronic progressive multiple sclerosis, hairy cell leukemia, systemic mastocytosis, and histiocytosis (including Erdheim–Chester disease and Langerhans cell histiocytosis). After a 2-hour intravenous infusion of cladribine 0.14 mg/kg/day, the mean maximum plasma drug concentration was 198 nmol/L. Intracellular concentrations of phosphorylated cladribine derivatives exceed plasma concentrations 128- to 375-fold. Cladribine penetrates into the CSF. The terminal elimination half-life (6.7 hours) is long, which suggests that the drug may be administered intermittently without loss of efficacy. The volume of distribution of cladribine is 9.2 L/kg. |
| References | [1] J.C Sipe, J. S Romine, R. McMillan, E. Beutler, J. C. Sipe, J. S. Romine, J. Zyroff (1994) Cladribine in treatment of chronic progressive multiple sclerosis, 344, 9-13 [2] Alan Saven, Carol Burian (1999) Cladribine Activity in Adult Langerhans-Cell Histiocytosis, 93, 4125-4130 [3] https://en.wikipedia.org/wiki/Cladribine [4] Harriet M. Bryson, Eugene M. Sorkin (1993) Cladribine: A Review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in haematological malignancies, 46, 872-894 |
| Description | Cladribine, an adenosine deaminase inhibitor, was introduced in the United States as asingle intravenous treatment for hairy cell leukemia. The incorporation of a chlorine atom atthe 2-position of deoxyadenosine renders cladribine more resistant to enzymatic attack byadenosine deaminase, resulting in a more prolonged cytotoxic effect. Cladribine efficientlycrosses lymphocyte and monocyte cell membranes and is metabolized in cells to thebiologically active triphosphate, which inhibits DNA synthesis. While most antineoplasticdrugs are active primarily against dividing cells, cladribine destroys both resting andproliferating cells. Its potential uses in the treatment of autoimmune hemolytic anemia,multiple sclerosis, chronic lymphocytic leukemia and various lymphomas have also beenevaluated. |
| Chemical Properties | White Crystalline Solid |
| Originator | Johnson & Johnson (U.S.A.) |
| Uses | 2-Chloro-2′-deoxyadenosine (2-CdA) is a chlorinated purine nucleoside with activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL) and multiple myeloma (MM). 2-CdA resists ADA degradation and is phosphorylated to CdATP in lymphocytes. CdATP incorporation into DNA induces strand breaks and the activation of apoptosis. 2-CdA may also be used in studies involving the inhibition of DNA polymerase(s). Cladribiane, like fludarabine, is a prodrug that is must be phosphorylated intracellularly to the monophosphate by the nuclear/cytosol enzyme deoxycytidine kinase (dCK) and possibly by the mitochondrial enzyme deoxyguanosine kinase (dGK). |
| Uses | It is a substituted purine nucleoside with antileukemic activity |
| Indications | Cladribine (Leustatin) is a synthetic purine nucleosidethat is converted to an active cytotoxic metabolite bythe enzyme deoxycytidine kinase. Like the other purineantimetabolites, it is relatively selective for both normaland malignant lymphoid cells and kills resting as well asdividing cells by mechanisms that are not completelyunderstood. The drug is highly active against hairy cell leukemia,producing complete remissions in more than 60% of patientstreated with a single 7-day course. Activity hasalso been noted in other low-grade lymphoid malignancies.The major side effect is myelosuppression. |
| Definition | ChEBI: 2'-Deoxyadenosine in which the hydrogen at position 2 on the purine ring has been substituted by chlorine. It inhibits the synthesis and repair of DNA, particularly in lymphocytes and monocytes, and is used as an antimetabolite antineoplastic drug for thetreatment of lymphoid malignancies including hairy-cell leukaemia and chronic lymphocytic leukaemia. |
| Manufacturing Process | Manufacturing process for Cladribine includes these steps as follows: Preparation of 2',3',5'-O-triacetyl guanosine;Preparation of 9-(2',3',5'-O-triacetyl-β-D-ribofuranosyl)-2-amino-6-chloropurine;Preparation of 9-(2',3',5'-O-triacetyl-β-D-ribofuranosyl)-2,6-dichloropurine;Preparation of 2-chloroadenosine;Preparation of 2-chloro-(3',5'-O-tetraisopropyldisiloxyl)adenosine; Preparation of 2-chloro-2'-O-phenoxythiocarbonyl-(3',5'-O-tetraisopropyldisiloxyl)adenosine; Preparation of 2-chloro-2'-deoxy-(3',5'-O-tetraisopropyldisiloxyl)adenosine; Preparation of 2-chloro-2'-deoxy-adenosine. |
| Brand name | Leustatin (Ortho Biotech). |
| Therapeutic Function | Cytostatic |
| General Description | The drug is available in a 10-mg or 10-mL single-use vialfor IV use. Cladribine is used for chronic lymphocyticleukemia, hairy cell leukemia, and non-Hodgkin’s lymphoma.The mechanism of action of this purine deoxyadenosineanalog involves incorporation into DNA resultingin inhibition of DNA chain extension and inhibitionof DNA synthesis and function. This incorporation intoDNA occurs via the triphosphate metabolite active species.The 2-chloro group on the adenine ring produces resistanceto breakdown by adenosine deaminase. Resistance to the anticancereffects can occur because of decreased expressionof the activating enzyme or overexpression of the catabolicenzymes. Oral bioavailability is variable and averages about50%. The drug crosses the blood-brain barrier; however,CSF concentrations reach only 25% of those in plasma. Thedrug is selectively activated inside the cell, and intracellularconcentrations of phosphorylated metabolites exceed thosein plasma. Toxicities include myelosuppression, neutropenia,immunosuppression, fever, nausea, and vomiting. |
| Biochem/physiol Actions | Deoxyadenosine analog resistant to adenosine deaminase; antileukemic with immunosuppressive activity |
| Clinical Use | Antineoplastic agent: Hairy cell leukaemia (HCL) Chronic lymphocytic leukaemia (CLL) in patients who have failed to respond to standard regimens. |
| Drug interactions | Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine - increased risk of agranulocytosis. Antivirals: avoid with lamivudine. Caution when administering with any other immunosuppressive or myelosuppressive therapy |
| Metabolism | Cladribine is extensively distributed and penetrates into the CNS. Cladribine is phosphorylated within cells by deoxycytidine kinase to form 2-chlorodeoxyadenosine-5′-monophosphate which is further phosphorylated to the diphosphate by nucleoside monophosphate kinase and to the active metabolite 2-chlorodeoxyadenosine-5′-triphosphate (CdATP) by nucleoside diphosphate kinase. CdATP inhibits DNA synthesis and repair, particularly in lymphocytes and monocytes There is little information available on the route of excretion of cladribine in man. An average of 18% of the administered dose has been reported to be excreted in urine of patients with solid tumours during a 5-day continuous intravenous infusion. |
| storage | Store at +4°C |
Cladribine Preparation Products And Raw materials
| Raw materials | Chloroform-->Silica gel-->Furan-->2,6-Dichloropurine-->4-Dimethylaminopyridine-->Tributyltin Hydride-->[1,2-Bis(diphenylphosphino)ethane]dichloropalladium(II)-->Sodium chloride-->ABIN-->1,1,3,3-TETRAISOPROPYLDISILOXANE |
