The purpose of this book is to propose a new strategy to heal human cancer completely with two
entirely new drug compounds exploiting cancer's Warburg effect characterized by a defective
mitochondrial aerobic respiration substituted for by cytosolic aerobic fermentation glycolysis
of glucose into L-(+)-lactic acid. The two essentially new drugs P(op)T(est)162 and PT167 were
discovered and developed by Andreas J. Kesel and internationally patented by PopTest Oncology
LLC Palisades Therapeutics. The in vitro antineoplastic highly efficacious drug PT167
represents a covalent combination of PT162 and PT166. The intermediate drug PT166 is an
entirely new colchic(in)oid derivative synthesized from colchicine. PT166's structure was
determined by X-ray crystallography. PT162 and PT167 were active in vitro versus 60 cancer cell
lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer
cell testing. PT162 and PT167 both not only stop the growth of cancer cells to ±0%
(cancerostatic effect) but completely kill all 60 cancer cells to a level of -100%
(tumoricidal effect). PT162 and PT167 induce mitochondrial apoptosis (under cytochrome c
release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function
which results in a decrease of cancer's dysregulated cyclin D1 and an induction of the cell
cycle-halting cyclin-dependent kinase inhibitor p21Waf1 p21Cip1.It was found that compound 1
(PT162 NSC 796018) a new compound never synthesized before [according to Chemical Abstracts
Service (CAS®) SciFinder® search] induced apoptosis in all cell lines of the National Cancer
Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell 5-dose testing
excluding leukemia cell lines in the micromolar range of growth inhibition 50% (GI50). The
author decided to merge compound 1 (PT162 NSC 796018) with the colchic(in)oid compound 2
(PT166 NSC 750423) which showed submicromolar GI50 in the NCI DTP 60-cancer cell 5-dose
testing but did not induce cancer cell apoptosis. Compound 2 (PT166 NSC 750423) was
synthesized from colchicine and thiosemicarbazide in an one-step procedure and represents a new
compound never synthesized before [according to Chemical Abstracts Service (CAS®) SciFinder®
search] just as compound 1 (PT162 NSC 796018). Compound 1 (PT162 NSC 796018) reacted with
compound 2 (PT166 NSC 750423) under impact of sodium hydroxide (NaOH) to give compound 3.
Compound 3 (PT167 NSC 799315) a new compound never synthesized before [according to Chemical
Abstracts Service (CAS®) SciFinder® search] showed submicromolar GI50 in the NCI DTP 60-cancer
cell 5-dose testing constantly in most cell lines including leukemia cells. Importantly
compound 3 (PT167 NSC 799315) was able to induce apoptosis in all investigated cancer cells
including leukemia cell lines with a Mean of Inhibition Data (MID) for total growth inhibition
(TGI growth inhibition 100%) of 4.57 µM and a MID for lethal concentration 50% (LC50) of
15.85 µM. The author reports here the chemistry and NCI DTP 60-cancer cell 5-dose testing data
for compound 1 (PT162 NSC 796018) compound 2 (PT166 NSC 750423) and compound 3 (PT167 NSC
799315) and demonstrates the apoptotic release of cytochrome c into the cytosol and activation
of effector caspases induced by compounds 1 and 3. The author proposes that compound 1 and
compound 3 induce apoptosis according to the Warburg hypothesis of pre-damaged respiration as a
hallmark of cancer by exploiting the defect in mitochondrial cardiolipin-cytochrome c
association in cancer cells.
