Drug intelligence / Profile preview

cytarabine + all-trans retinoic acid + valproic acid

Development stage
Unknown
Lead developer
Norwegian Cancer Society
Modality
Small Molecules
Administration
Oral, Subcutaneous
01

Overview

This is a combination therapy consisting of three drugs—cytarabine, all-trans retinoic acid (ATRA), and valproic acid—used primarily for the treatment of acute myeloid leukemia (AML), especially in patients unfit for intensive chemotherapy due to age or comorbidities. - **Cytarabine** is a nucleoside analog that inhibits DNA polymerase, leading to impaired DNA synthesis and cell death in rapidly dividing cells. - **All-trans retinoic acid (ATRA)** acts as an agonist at the retinoic acid receptor-alpha, promoting differentiation of leukemic cells. - **Valproic acid** is a histone deacetylase inhibitor with epigenetic effects that can induce differentiation and apoptosis in malignant cells. The combination has been shown to stabilize disease by improving peripheral blood counts and prolonging survival in some AML patients who are not candidates for standard intensive regimens[1][2][4]. The regimen generally involves continuous administration of valproic acid, intermittent oral ATRA, and low-dose subcutaneous cytarabine[1][2]. Complete hematological remission occurs rarely; most benefit comes from disease stabilization with relatively low toxicity[1][2]. In vitro studies suggest anti-proliferative effects on both leukemic and stromal support cells[5].

Other names
cytarabine + ATRA + valproic acidcytarabine + all-trans retinoic acid + VPA
02

Targets

RARA (Retinoic acid receptor alpha)POLA1 (DNA polymerase alpha)HDAC (HDAC family)

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