DDInter1762 DDInter255
Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time.[A229848, A229858, L32033] Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration.[A229853, A229888, A229923, L32033] Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual
Busulfan is a bifunctional alkylating agent, having a selective immunosuppressive effect on bone marrow. It is not a structural analog of the nitrogen mustards. It has been used in the palliative treatment of chronic myeloid leukemia (myeloid leukemia, chronic), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
Temozolomide {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Busulfan
Temozolomide {u} (Compound) is included by {v} (Pharmacologic Class) Alkylating Activity
Alkylating Activity {u} (Pharmacologic Class) includes {v} (Compound) Busulfan
Temozolomide {u} (Compound) downregulates {v} (Gene) CHMP4A
CHMP4A {u} (Gene) is downregulated by {v} (Compound) Busulfan
Temozolomide {u} (Compound) causes {v} (Side Effect) Amenorrhoea
Amenorrhoea {u} (Side Effect) is caused by {v} (Compound) Busulfan
Temozolomide {u} (Compound) downregulates {v} (Gene) CHMP4A
CHMP4A {u} (Gene) is regulated by {v} (Gene) GSTM1
GSTM1 {u} (Gene) is bound by {v} (Compound) Busulfan
Temozolomide {u} (Compound) downregulates {v} (Gene) S100A13
S100A13 {u} (Gene) regulates {v} (Gene) MCOLN1
MCOLN1 {u} (Gene) is upregulated by {v} (Compound) Busulfan
Temozolomide {u} (Compound) treats {v} (Disease) brain cancer
brain cancer {u} (Disease) is associated with {v} (Gene) MYC
MYC {u} (Gene) is downregulated by {v} (Compound) Busulfan
Temozolomide {u} (Compound) downregulates {v} (Gene) S100A13
S100A13 {u} (Gene) is regulated by {v} (Gene) NMT1
NMT1 {u} (Gene) is upregulated by {v} (Compound) Busulfan
Temozolomide {u} (Compound) downregulates {v} (Gene) S100A13
S100A13 {u} (Gene) is regulated by {v} (Gene) TXNRD1
TXNRD1 {u} (Gene) is downregulated by {v} (Compound) Busulfan
Temozolomide {u} (Compound) treats {v} (Disease) malignant glioma
malignant glioma {u} (Disease) is associated with {v} (Gene) GSTP1
GSTP1 {u} (Gene) is bound by {v} (Compound) Busulfan
Temozolomide (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Busulfan (Compound)
Temozolomide (Compound) is included by Alkylating Activity (Pharmacologic Class) and Alkylating Activity (Pharmacologic Class) includes Busulfan (Compound)
Temozolomide (Compound) downregulates CHMP4A (Gene) and CHMP4A (Gene) is downregulated by Busulfan (Compound)
Temozolomide (Compound) causes Amenorrhoea (Side Effect) and Amenorrhoea (Side Effect) is caused by Busulfan (Compound)
Temozolomide (Compound) downregulates CHMP4A (Gene) and CHMP4A (Gene) is regulated by GSTM1 (Gene) and GSTM1 (Gene) is bound by Busulfan (Compound)
Temozolomide (Compound) downregulates S100A13 (Gene) and S100A13 (Gene) regulates MCOLN1 (Gene) and MCOLN1 (Gene) is upregulated by Busulfan (Compound)
Temozolomide (Compound) treats brain cancer (Disease) and brain cancer (Disease) is associated with MYC (Gene) and MYC (Gene) is downregulated by Busulfan (Compound)
Temozolomide (Compound) downregulates S100A13 (Gene) and S100A13 (Gene) is regulated by NMT1 (Gene) and NMT1 (Gene) is upregulated by Busulfan (Compound)
Temozolomide (Compound) downregulates S100A13 (Gene) and S100A13 (Gene) is regulated by TXNRD1 (Gene) and TXNRD1 (Gene) is downregulated by Busulfan (Compound)
Temozolomide (Compound) treats malignant glioma (Disease) and malignant glioma (Disease) is associated with GSTP1 (Gene) and GSTP1 (Gene) is bound by Busulfan (Compound)