1276553-09-3 Usage
Biological Activity
the constitutive activation of phosphoinositide 3-kinase (pi3k) occurs frequently in many human tumors through either gene mutation in the p110a catalytic subunit of pi3k or functional loss of tumor suppressor pten. patients with small-cell lung cancer have very poor prognosis and survival rates such that an effective targeted therapy is in strong demand for these patients. pf-4989216 is a selective oral pi3k inhibitor.
in vitro
pf-4989216 inhibited pi3k downstream signaling and led to apoptosis induction, and inhibition in cell viability, transformation, and xenograft tumor growth in small-cell lung cancer (sclc) harboring pik3ca mutation. in sclc with pten loss, pf-4989216 also inhibited pi3k signaling but did not induce bcl2-interacting mediator-mediated apoptosis nor was there any effect on cell viability or transformation [1].
in vivo
the mouse in vivo results indicate a good correlation between in vitro and in vivo efficacy, and further confirm that pf-4989216 is an effective drug candidate capable of inducing antitumor activity in mice bearing human sclc tumors with pik3ca mutation [1].
IC 50
2 nm, 142 nm, 65 nm, 1 nm, and 110 nm for p110α, p110β, p110γ, p110δ, and vps34, respectively.
references
[1] walls m, baxi sm, mehta pp, liu kk, zhu j, estrella h, li c, zientek m, zong q, smeal t, yin mj. targeting small cell lung cancer harboring pik3ca mutation with a selective oral pi3k inhibitor pf-4989216. clin cancer res. 2014 feb 1;20(3):631-43.
Check Digit Verification of cas no
The CAS Registry Mumber 1276553-09-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,7,6,5,5 and 3 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1276553-09:
(9*1)+(8*2)+(7*7)+(6*6)+(5*5)+(4*5)+(3*3)+(2*0)+(1*9)=173
173 % 10 = 3
So 1276553-09-3 is a valid CAS Registry Number.
1276553-09-3Relevant articles and documents
Development of scalable syntheses of selective PI3K inhibitors
Huang, Qinhua,Richardson, Paul F.,Sach, Neal W.,Zhu, Jinjiang,Liu, Kevin K.-C.,Smith, Graham L.,Bowles, Daniel M.
, p. 556 - 564 (2011/12/02)
On the basis of a more practical and scalable route to an iodothiophene, an efficient and reliable synthesis has been developed for three selective PI3K inhibitors. From this advanced intermediate, the three title compounds were each prepared in five additional steps. Key learnings also include: high throughput experimentation (HTE) screening toward a more robust Suzuki coupling, a more efficient triazole synthesis, and an acid/base cleanup developed to purify the final compounds. The final enabled synthesis required no column chromatography.
