Latest Breast Cancer Drug With Modest Gain

choi

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Peter Landers, New Breast Cancer Drug Found Deep in the Sea. Wall Street Journal, Jan. 4, 2010.
http://online.wsj.com/article/SB10001424052748704111504576059772498413328.html
("A study found it [Halaven] extended the life of patients with advanced breast cancer by about two-and-1/2 months, to 13 months")

My comment:
(a) Eisai Co., Ltd. エーザイ株式会社
(a public company; headquarters Tokyo; established in 1941 by Toyoji NAITO 内藤 豊次 as Nohon Eisai Co., Ltd. 日本衛材（衛生材料の略。具体的には絆創膏や包帯の事))
ja.wikipedia.org
(b) eribulin
http://en.wikipedia.org/wiki/Eribulin

(c) Yoshito KISHI 岸 義人, Department of Chemistry and Chemical Biology, Harvard University.
http://www.chem.harvard.edu/research/faculty/yoshito_kishi.php
(d) Catharanthus
http://en.wikipedia.org/wiki/Catharanthus
(the genus name for Madagascar periwinkle)

Note: Madagascar periwinkle is an annual bedding plant we see everywhere in US and Taiwan alike.

(i) vincristine
http://en.wikipedia.org/wiki/Vincristine
(approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin)

Quote:

Vincristine is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name.

"Vincristine binds to tubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests mitosis in metaphase. The vinca alkaloids therefore affect all rapidly dividing cell types including cancer cells, but also intestinal epithelium and bone marrow.

(e) Mechanism of the Gleevec.

Most chronic myelogenous leukemia (CML) patients share a distinctive feature: Philadelphia chromosome, so named because it was first discovered and described in 1960 by two scientists from Philadelphia. The reciprocal translocation switches ends of chromosomes 9 and 22 with each other (the resultant chromosome 22 is the Philadelphia chromosome). As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9.

The abl stands for "Abelson", the name of a leukemia VIRUS (in mouse)  which carries a similar protein whose gene the virus grabbed from a host in ancient time to help itself proliferate. ABL (all upper cases) is the normal counterpart in almost all living cells that performs vital functions--basically an enzyme that can add a phosphate group to a certain tyrosine residue of a tyrosine kinase, therefore activating that kinase. In Philadelphia chromosome, the ABL portion of the fusion protein is stuck in a perpetually active position, which somehow causes cancer. (Why? Nobody knows.)

Gleevec specifically binds to, blocks and inactivates the ABL portion of the fusion protein.

(f) Takashi OWA 大和 隆志 (東京大学大学院薬学系研究科博士)
(g)
(i) For ramamycine, see sirolimus
http://en.wikipedia.org/wiki/Sirolimus
(an immunosuppressant drug used to prevent rejection in organ transplantation; was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter Island — an island also known as "Rapa Nui", hence the name)

(ii) The origin of "Rapa Rui" name:
http://www.netaxs.com/~trance/def.html

Compare
Rapa Iti
http://en.wikipedia.org/wiki/Rapa_Iti

Rapa Iti was originally called simply Rapa. Iti ("small" in the local Polynesian language) was added to distinguish Rapa Rui, which was actually named after Rapa (Iti).

(iii) mammalian target of rapamycin
http://en.wikipedia.org/wiki/Mammalian_target_of_rapamycin
(mTOR; a serine/threonine protein kinase)

A serine/threonine protein kinase is a (protein) kinase  which is activated by adding a phosphate to a certain serine or threonine of that kinase--as opposed to tyrosine of a tyrosine kinase--and activate the kinase.

The serine, threonine and tyrosine are amino acids, components of a protein.


(h) Sidebar:
* Cinchona
http://en.wikipedia.org/wiki/Cinchona
(Carolus "Carl" Linnaeus named the tree in 1742 after a Countess of Chinchon, the wife of a viceroy of Peru, who, in 1638, was introduced by natives to the medicinal properties of the bark)

Translated as 金雞納樹 in Taiwan.

* Compare chemical structures of aspirin (acetylsalicylic acid chemically)
http://en.wikipedia.org/wiki/Aspirin
and
salicylic acid
http://en.wikipedia.org/wiki/Salicylic_acid
, and you will learn where the acetyl group (CH3-COO) is added to the latter.

* cyclosporin
http://en.wikipedia.org/wiki/Cyclosporin
(Initially isolated from the fungus Tolypocladium inflatum isolated from a soil sample obtained by Sandoz scientists at Hardangervidda, Norway in 1969, ciclosporin is a cyclic nonribosomal peptide of 11 amino acids)

Translated as 環孢靈. 環 (or cyclo- in English name), due to its "cyclic" structre.

* exenatide
http://en.wikipedia.org/wiki/Exenatide
(marketed as Byetta; a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster that was first isolated by Dr. John Eng in 1992 while working at the Veterans Administration Medical Center in the Bronx, New York; made up of 39 amino acids; injected subcutaneously)

John Eng MD, an endocrinologist, is Asian. His publication to report discovery did not speculate about its function in the animal.
Eng J et al, Isolation and Characterizationo f Exendin-4, an Exendin-3 Analogue, from Heloderma suspecturn Venom; Further evidence for an exendin receptor on dispersed acini from Guinea Pig Pancreas. J. Biol Chem
267: 7402-7405 (1992).
http://www.jbc.org/content/267/11/7402.full.pdf

Gila monster
http://en.wikipedia.org/wiki/Gila_monster
(native to the southwestern United States and northerwestern Mexico; A heavy, slow-moving lizard, up to 60 centimetres (2.0 ft) long; The name Gila refers to the Gila River Basin in Arizona, where they were once plentiful; section 3.2 Venom)

What is the function of the hormone for Gila monster itself, as opposed to humans? Nobody knows.


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