Drug Development Pipeline

  Target
Discovery
Pre-clinical
IND
Phase I
Ph II
Ph III
NDA
YN968D1
VEGFr
               
AL6802
EGFR
             
AL3810
Multi-PTK
             
AL3818
VEGFr,FGFr
               
AL8326
Multi-PTK
           
AL2846
c-Met
           

YN968D1(Apatinib)
Angiogenesis inhibitors are of considerable interests for the treatment of cancer. Market approval of Avastin, a monoclonal VEGF antibody as one of angiogenesis inhibitors for colorectal, lung and breast cancer further validates this mechanism. Further market approvals of small molecules, Nexavar and Sutent have firmly supported this approach.

We are actively searching for angiogenesis inhibitors. Our scientists have synthesized and discovered a series of novel small molecule angiogenesis inhibitors. YN968D1 (Apatinib) has been selected for further preclinical and clinical studies. This compound shows very good in vitro and in vivo activities agaist various tumor cell line. It has also shown major protein tyrosine kinase (PTK) inhibition on VEGFr2 and Ret and mild inhibition on c-Kit and c-SRC. Its toxicity profile is very modest in rats and dogs.

Compound
Kinase
IC50 (nM)



YN968D1
Ret(h)
13
KDR(h)
1
PDGFRα(h)
>1000
cKit(h)
429
cSRC(h)
530
HUVEC-cell based
30

YN968D1 (Apatinib) is the most selective small molecule VEGFr inhibitor in the industry to date. It can be a potential “Oral Avastin”.

YN968D1 Chinese Phases I & II have finished and Chinese Phase III is on going.

AL6802
Our scientists recently have discovered the AL68 series of small molecules that have very potent activity at in vitro human cancer cell proliferation assay and in vivo human cancer cell A431 xenograft model. AL6802 has shown good in vivo activity against A431 and NSCLC A549 xenograft experiments. This compound is targeting epidermal growth factor receptor (EGFR) for cancer treatment.

AL6802 has comparable activity both against in vitro cell proliferation MTT assay and against in vivo human A431 xenograft and human NSCLC A549 to commercial marketed products. It has been chosen for further preclinical development.

AL3810
Our scientists have synthesized and discovered a series of novel small molecule PTK inhibitors. AL3810 has been selected for further preclinical studies. This compound shows very good in vivo activities in human colon cancer HT29 xenograft. It shows significant tumor regression during the experiment. AL3810 also demonstrated superior in vivo efficacy in human liver cancer Bel-7402 xenograft experiment. AL3810 as a multi-PTK inhibitor selectively inhibits VEGFR, c-Kit, c-Raf and PDGFR kinases; Phase I clinical trials are ongoing.

AL3818
Our scientists have synthesized and discovered a series of novel small molecule PTK inhibitors. AL3818 has been selected for further preclinical studies. This compound shows very good in vivo activities in human colon cancer HT29 and NSCLC A549 xenografts. It generates great efficacy at very lower dose range and it shows significant tumor regression during experiments. AL3818 also demonstrated superior in vivo efficacy in human liver cancer Bel-7402 xenograft experiment. AL3818 selectively inhibits VEGFR and FGFR kinases; Phase I clinical trials are ongoing.

AL8326
AL8326 is a multikinase inhibitor and mainly inhibits receptor tyrosine kinases (RTK) of c-Kit, FGF, VEGF (Flt1, Flt4 and KDR), PDGF and Ret. It has been shown remarkable efficacy in several xenograft models. AL8326 also has been generally demonstrated better in vivo activities comparing with sunitinib or sorafenib in xenograft models of human NSCLC 95D, liver cancer Bel-7402, glioblastoma SHG44, renal cell carcinoma (RCC) 786-O, AML HL60, U937 and ovarian cancer SKOV3. AL8326 pharmacokinetic profiles on rats are also favorable with oral half life at 1.8 hour and bioavailability at 28.8%. Further IND enabling studies of AL8326 are on going.

AL2846
AL2846 is a c-Met receptor tyrosine kinase (RTK) inhibitor and it also inhibits other RTKs of Flt4, KDR and Ron. It has demonstrated remarkable activities in various xenograft models of human gastric cancer SGC 7901, human breast cancer MDA-MB-435, human colon cancer colo205 and human RCC-786-O. AL2846 also has good bioavailability and further preclincal studies of AL2846 are on going.