Cladribine

Bezeichnung:Cladribine

CAS-Nr4291-63-8

Englisch Name:Cladribine

CBNumberCB4222723

SummenformelC10H12ClN5O3

Molgewicht285.69

MOL-Datei4291-63-8.mol

Cladribine physikalisch-chemischer Eigenschaften

Schmelzpunkt	181-185 °C(lit.)
alpha	D25 -18.8° (c = 1 in DMF)
Siedepunkt	547.6±60.0 °C(Predicted)
Dichte	2.03±0.1 g/cm3(Predicted)
storage temp.	-20°C
Löslichkeit	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)
Aggregatzustand	White solid
Farbe	White to Pale Yellow
maximale Wellenlänge (λmax)	265nm(EtOH aq.)(lit.)
Merck	14,2337
Stabilität	Store in Freezer
InChIKey	PTOAARAWEBMLNO-HSUXUTPPSA-N
CAS Datenbank	4291-63-8(CAS DataBase Reference)

Sicherheit

Kennzeichnung gefährlicher	T
R-Sätze:	36/37/38-23/24/25
S-Sätze:	26-37/39-45-36-22
RIDADR	UN 2811 6.1 / PGIII
WGK Germany	3
RTECS-Nr.	AU7357560
HS Code	29349990
Giftige Stoffe Daten	4291-63-8(Hazardous Substances Data)
Toxizität	LD50 intraperitoneal in mouse: 150mg/kg

Gefahreninformationscode (GHS)

Cladribine Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
R23/24/25:Giftig beim Einatmen, Verschlucken und Berührung mit der Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S37/39:Bei der Arbeit geeignete Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
S22:Staub nicht einatmen.
Beschreibung
Cladribine, an adenosine deaminase inhibitor, was introduced in the United States as a single intravenous treatment for hairy cell leukemia. The incorporation of a chlorine atom at the 2-position of deoxyadenosine renders cladribine more resistant to enzymatic attack by adenosine deaminase, resulting in a more prolonged cytotoxic effect. Cladribine efficiently crosses lymphocyte and monocyte cell membranes and is metabolized in cells to the biologically active triphosphate, which inhibits DNA synthesis. While most antineoplastic drugs are active primarily against dividing cells, cladribine destroys both resting and proliferating cells. Its potential uses in the treatment of autoimmune hemolytic anemia, multiple sclerosis, chronic lymphocytic leukemia and various lymphomas have also been evaluated.
Chemische Eigenschaften
White Crystalline Solid
Originator
Johnson & Johnson (U.S.A.)
Verwenden
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).
Verwenden
It is a substituted purine nucleoside with antileukemic activity
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 the treatment of lymphoid malignancies including hairy-cell leukaemia and chronic lymphocytic leukaemia.
Indications
Cladribine (Leustatin) is a synthetic purine nucleoside that is converted to an active cytotoxic metabolite by the enzyme deoxycytidine kinase. Like the other purine antimetabolites, it is relatively selective for both normal and malignant lymphoid cells and kills resting as well as dividing cells by mechanisms that are not completely understood.
The drug is highly active against hairy cell leukemia, producing complete remissions in more than 60% of patients treated with a single 7-day course. Activity has also been noted in other low-grade lymphoid malignancies. The major side effect is myelosuppression.
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.
Trademarks
Leustatin (Ortho Biotech).
Therapeutic Function
Cytostatic
Allgemeine Beschreibung
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.
Arzneimittelwechselwirkung
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
Stoffwechsel
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.
Lager
Store at +4°C

Cladribine Upstream-Materialien And Downstream Produkte

Cladribine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

4291-63-8, Cladribine Verwandte Suche:

Send Inquriy