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. Author manuscript; available in PMC: 2014 Apr 30.
Published in final edited form as: Cancer Res. 2013 Oct 4;73(20):6149–6163. doi: 10.1158/0008-5472.CAN-12-4617

Table 1.

List of drugs of breast cancer brain metastasis that were repositioned and their BBB permeability

Drug target Drug name Approval
status
Approved indications "Rule of Five"
for CNS drugsa
BBB
permeability
HDAC1, HDAC2 Vorinostat Approved Cutaneous T-cell lymphoma 2009, Clin Can Res (26)
KDR, RET Sunitinib Approved Gastrointestinal stromal tumor (GIST); advanced renal cell carcinoma (RCC); advanced pancreatic neuroendocrine tumors (pNET) 2009, Lancet Oncol (45)
KDR Cabozantinib(XL184) Phase II/III Breast cancer (phase II); metastatic prostate cancer (phase II); carcinoid tumor (phase II); pancreatic neuroendocrine tumor (phase II); thyroid cancer (phase III); glioblastoma multiforme (phase II); carcinoma, non-small cell lung (phase II); astrocytic tumors (phase II) 2011, J Clin Oncol (28)
RET Imatinib Approved Chronic myeloid leukemia (CML)
RAF1, KDR Sorafenib Approved Hepatocellular carcinoma; renal cell carcinoma
Pazopanib Approved Renal cell carcinoma 2010, Clin Can Res (27)
FYN Dasatinib Approved Chronic myeloid leukemia (CML); Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) 2008, Blood (44)
NFKB1 Dexamethasone Approved Allergic states; dermatologic diseases; endocrine disorders; gastrointestinal diseases; hematologic disorders; neoplastic diseases; nervous system; ophthalmic diseases; renal diseases; respiratory diseases; rheumatic disorders
Thalidomide Approved Multiple myeloma; erythema nodosum leprosum
Pranlukast Phase III Chronic sinusitis
GRB2 Pegademase Approved Adenosine deaminase (ADA) deficiency
IKBKB Auranofin Approved Rheumatoid arthritis
Arsenite Not approved
VIM Acetate ion Not approved
PHGDH NADH Not approved
a

The "Rule of Five" is so named because all the essential physical properties of compounds are parameters of five. According to this rule, a good absorption and permeability are likely if: molecular weight is ≤500; oil/water distribution coefficient (LogP) is ≤5; hydrogen bond donors ≤5 (expressed as the sum of OHs and NHs); hydrogen bond acceptor ≤10 (expressed as the sum of Ns and Os); and number of rotatable bonds ≤10.