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|
| Novel Paradigm of Metabolic Regulation |
Convention of white, brown adipocytes and muscles |
| Sonic Hedgehog, human |
080-12 |
5 µg / 25 µg / 100 µg |
$235 / $995 / $3,795 |
| mAb, human sHh |
080-28 |
5 µg / 25 µg / 1000 µg |
$275 / $975 / $2,775 |
| SAG (SMO agonist) |
080-59 |
1 mg / 5 mg / 25 mg |
$149 / $449 / $1,349 |
| Purmorphamine (SMO agonist) |
080-60 |
5 mg / 25 mg / 100 mg |
$99 / $359 / $1,139 |
| 25-hydroxycholesterol (agonist) |
080-61 |
5 mg / 25 mg / 100 mg |
$45 / $145 / $445 |
| 20-hydroxycholesterol (agonist) |
080-62 |
5 mg / 25 mg / 100 mg |
$40 / $140 / $640 |
| Cyclopamine (antagonist) |
080-63 |
5 mg / 25 mg / 100 mg |
$49 / $149 / $349 |
| Jervine (antagonist) |
080-64 |
1 mg / 5 mg / 25 mg |
$99 / $399 / $1,399 |
| GDC-0449 (SMO antagonist) |
080-65 |
5 mg / 25 mg / 100 mg |
$94 / $294 / $994 |
| LDE225 (SMO antagonist) |
080-66 |
2 mg / 10 mg / 50 mg |
$85 / $225 / $625 |
| IPI-926 (antagonist) |
080-67 |
1 mg / 5 mg / 25 mg |
$126 / $426 / $1,426 |
| WNT-3a, human |
080-01 |
5 µg / 25 µg / 100 µg |
$245 / $1,095 / $3,995 |
| WNT-3a, mouse |
080-02 |
5 µg / 25 µg / 100 µg |
$195 / $995 / $3,495 |
| WNT-5a, human |
080-03 |
5 µg / 25 µg / 100 µg |
$345 / $1,395 / $4,995 |
| WNT-5a, mouse |
080-04 |
5 µg / 25 µg / 100 µg |
$245 / $1,145 / $3,995 |
| DKK-1, human |
080-16 |
25 µg / 100 µg / 500 µg |
$215 / $895 / $3,135 |
| DKK-1 Fc fusion, human |
080-15 |
50 µg / 250 µg / 1000 µg |
$295 / $1,195 / $3,995 |
| Frizzled-8 Fc fusion, human |
080-18 |
50 µg / 250 µg / 1000 µg |
$195 / $905 / $1,950 |
| Human/Mouse TCF Reporter Cell |
080-52 / 080-53 |
5 million cells / 5 million cells |
$3,999 / $3,999 |
| R-spondin-1, human |
080-19 |
5 µg / 25 µg / 100 µg |
$91 / $291 / $991 |
| CHIR99021 (GSK-3 inhibitor) |
080-56 |
2 mg / 10 mg / 50 mg |
$93 / $293 / $993 |
| IWP-2 ( Porcupine inhibitor) |
080-57 |
2 mg / 10 mg / 50 mg |
$62 / $162 / $582 |
| XAV-939 (Tankyrase inhibitor) |
080-58 |
2 mg / 10 mg / 50 mg |
$59 / $159 / $459 |
| Activin A, human |
080-05 |
5 µg / 25 µg / 100 µg |
$175 / $745 / $1,975 |
| TGF-β1, human |
080-09 |
5 µg / 25 µg / 100 µg |
$199 / $759 / $1,999 |
| BMP-4, human |
080-06 |
5 µg / 25 µg / 100 µg |
$185 / $895 / $3,195 |
| BMP-2, human |
080-54 |
5 µg / 25 µg / 100 µg |
$122 / $522 / $1,422 |
| BMP-7, human |
080-55 |
5 µg / 25 µg / 100 µg |
$127 / $527 / $1,527 |
| Follistatin Fc fusion, human |
080-22 |
50 µg / 250 µg /1000 µg |
$175 / $745 / $1,975 |
| Noggin, human |
080-24 |
50 µg / 250 µg /1000 µg |
$195 / $895 / $2,995 |
| Dorsomorphin (ALK-2,3,6 inhibitor) |
080-68 |
2 mg / 10 mg / 50 mg |
$69 / $169 / $569 |
| SB 431542 (ALK-4,5,7 inhibitor) |
080-69 |
2 mg / 10 mg / 50 mg |
$49 / $149 / $449 |
| A83-01 |
080-70 |
2 mg / 10 mg / 50 mg |
$83 / $238 / $638 |
| ALK-5 Inhibitor |
080-71 |
2 mg / 10 mg / 50 mg |
$55 / $155 / $455 |
| LDN-193189 |
080-72 |
2 mg / 10 mg / 50 mg |
$89 / $219 / $569 |
| LY-364947 |
080-73 |
2 mg / 10 mg / 50 mg |
$47 / $147 / $547 |
Recently, a new metabolic paradigm has been postulated based on the development of white vs. brown adipose tissue. Growth and differentiation factors involved in embryonic development are implicated in the conversion of white and brown adipocytes as well as muscle. Phoenix Pharmaceuticals and its partner StemRD are offering top-quality products in this area.
Hepatocellular carcinoma (HCC) typically develop in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts (MF). Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent MF in hepatocarcinogenesis is unknown. Here we used human HCC samples, a mouse HCC model, and hepatoma cell/MF co-cultures to examine the hypothesis that Hh signaling modulates MF metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce HH-ligands to stimulate glycolysis in neighboring MF, resulting in release of MF-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCC.
Chan IS, Guy CD, Chen Y et al, Cancer Res. 2012 Oct 12.
Developmental genes are essential in the formation and function of adipose tissue and muscle. In
this issue of Cell, Teperino et al. demonstrate that noncanonical hedgehog signaling increases
glucose uptake into brown fat and muscle. Modulation of developmental pathways may serve
as a potential target for new treatments of diabetes and other metabolic disorders.
Kevin Y. Lee and C. Ronald Kahn, Cell, Volume 151, Issue 2, 248-250, 12 October 2012.
Diabetes, obesity, and cancer affect upward of 15%
of the world’s population. Interestingly, all three diseases
juxtapose dysregulated intracellular signaling
with altered metabolic state. Exactly which genetic
factors define stable metabolic set points in vivo
remains poorly understood. Here, we show that
hedgehog signaling rewires cellular metabolism.
We identify a cilium-dependent Smo-Ca2+-Ampk
axis that triggers rapid Warburg-like metabolic reprogramming
within minutes of activation and is
required for proper metabolic selectivity and flexibility.
We show that Smo modulators can uncouple
the Smo-Ampk axis from canonical signaling and
identify cyclopamine as one of a new class of ‘‘selective
partial agonists,’’ capable of concomitant inhibition
of canonical and activation of noncanonical
hedgehog signaling. Intriguingly, activation of the
Smo-Ampk axis in vivo drives robust insulin-independent
glucose uptake in muscle and brown
adipose tissue. These data identify multiple noncanonical
endpoints that are pivotal for rational design
of hedgehog modulators and provide a new therapeutic
avenue for obesity and diabetes.
Teperino R. et al, Cell, volume 151 issue 2, 414-426, 12 October 2012
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