PI3K-Inhibitors-Modulators-MCE

1、 HYPERLINK https:/www.MedChemE/Targets/PI3K.html PI3KPhosphoinositide 3-kinasePI3K (Phosphoinositide 3-kinase), via phosphorylation of the inositol lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P ), forms2the second messenger molecule phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P ) wh

2、ich recruits and activates pleckstrin3homology domain containing proteins, leading to downstream signalling events crucial for proliferation, survival and migration.Class I PI3K enzymes consist of four distinct catalytic isoforms, PI3K, PI3K, PI3K and PI3K.There are three major classes of PI3K enzym

3、es, being class IA widely associated to cancer. Class IA PI3K are heterodimeric lipidkinases composed of a catalytic subunit (p110, p110, or p110; encoded by PIK3CA, PIK3CB, and PIK3CD genes, respectively) anda regulatory subunit (p85).The PI3K pathway plays an important role in many biological proc

4、esses, including cell cycle progression, cell growth, survival, actinrearrangement and migration, and intracellular vesicular transport.www.MedChemE 12 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/Targets/PI3K.html PI3K HYPERLINK https:/www.MedChemE/Targets/

5、PI3K.html HYPERLINK https:/www.MedChemE/Targets/PI3K.html Inhibitors, HYPERLINK https:/www.MedChemE/Targets/PI3K.html HYPERLINK https:/www.MedChemE/Targets/PI3K.html Activators HYPERLINK https:/www.MedChemE/Targets/PI3K.html HYPERLINK https:/www.MedChemE/Targets/PI3K.html & HYPERLINK https:/www.MedC

6、hemE/Targets/PI3K.html HYPERLINK https:/www.MedChemE/Targets/PI3K.html Modulators HYPERLINK https:/www.MedChemE/plus-nortrachelogenin.html (+)-Nortrachelogenin(Wikstromol) Cat. No.: HY-N3171A HYPERLINK https:/www.MedChemE/rac-azd-6482.html (Rac)-AZD HYPERLINK https:/www.MedChemE/rac-azd-6482.html HY

7、PERLINK https:/www.MedChemE/rac-azd-6482.html 6482(Rac)-KIN-193) Cat. No.: HY-75124(+)-Nortrachelogenin (Wikstromol), apharmacologically ligand from from wikstroemiaindica, possesses antileukemic activity.(Rac)-AZD 6482 (Rac)-KIN-193) is the racemate ofAZD 6482. AZD 6482 is a potent and selective p1

8、10inhibitor with an IC of 0.69 nM.50Purity: 98%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 25 mgPurity: 97.92%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/s-pi3k-in-4.html (S)-PI3K-IN-4Cat. No.: HY-131345A HYPERLINK htt

9、ps:/www.MedChemE/1,3-Dicaffeoylquinic-acid.html 1,3-Dicaffeoylquinic HYPERLINK https:/www.MedChemE/1,3-Dicaffeoylquinic-acid.html HYPERLINK https:/www.MedChemE/1,3-Dicaffeoylquinic-acid.html acid(1,3-O-Dicaffeoylquinic acid; 1,5-Dicaffeoylquinic acid) Cat. No.: HY-N1412(S)-PI3K-IN-4 is a potent inhi

10、bitor of PI3K, withan IC of 2.3 nM. (S)-PI3K-IN-4 shows 38.3-,504.25-, and 4.93-fold selectivity for PI3K overPI3K, PI3K, and PI3K, respectively. (S)-PI3K-IN-4can be used for the research of cancer.1,3-Dicaffeoylquinic acid is a caffeoylquinic acidderivative that exhibits antioxidant activity andrad

11、ical scavenging activity.Purity: 99.79%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 98.85%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg HYPERLINK https:/www.MedChemE/1-Deoxynojirimycin.html 1-Deoxynojirimycin(Duvoglusta

12、t) Cat. No.: HY-14860 HYPERLINK https:/www.MedChemE/1-deoxynojirimycin-hydrochloride.html 1-Deoxynojirimycin HYPERLINK https:/www.MedChemE/1-deoxynojirimycin-hydrochloride.html HYPERLINK https:/www.MedChemE/1-deoxynojirimycin-hydrochloride.html hydrochloride(Duvoglustat hydrochloride) Cat. No.: HY-1

13、4860A1-Deoxynojirimycin (Duvoglustat) is a potent andorally active -glucosidase inhibitor.1-Deoxynojirimycin suppresses postprandial bloodglucose and is widely used for diabetes mellitus.1-Deoxynojirimycin possesses antihyperglycemic,anti-obesity, and antiviral features.1-Deoxynojirimycin hydrochlor

14、ide (Duvoglustathydrochloride) is a potent and orally active-glucosidase inhibitor. 1-Deoxynojirimycinhydrochloride suppresses postprandial bloodglucose and is widely used for diabetes mellitus.Purity: 98.0%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mgPurity: 98%Clinical Data: Ph

15、ase 2Size: 5 mg, 10 mg, 25 mg HYPERLINK https:/www.MedChemE/25-r-s-ruscogenin.html 25(R,S)-Ruscogenin HYPERLINK https:/www.MedChemE/25-r-s-ruscogenin.html HYPERLINK https:/www.MedChemE/3-Methyladenine.html 3-MethyladenineCat. No.: HY-N5136(3-MA) Cat. No.: HY-19312Ruscogenin suppresses HCC metastasis

16、 by reducingthe expression of MMP-2, MMP-9, uPA, VEGF andHIF-1 via regulating the PI3K/Akt/mTORsignaling pathway. And Ruscogenin alleviatesLPS-induced pulmonary endothelial cell apoptosisby su.3-Methyladenine (3-MA) is a PI3K inhibitor.3-Methyladenine is a widely used inhibitor ofautophagy via its i

17、nhibitory effect on class IIIPI3K.Purity: 99.84%Clinical Data: No Development ReportedSize: 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.83%Clinical Data: No Development ReportedSize: 50 mg, 100 mg, 200 mg, 500 mg HYPERLINK https:/www.MedChemE/740_Y-P.html 740 HYPERLINK https:/www.MedChemE/740_Y-P.html HYPE

18、RLINK https:/www.MedChemE/740_Y-P.html Y-P HYPERLINK https:/www.MedChemE/740_Y-P.html HYPERLINK https:/www.MedChemE/740-y-p-tfa.html 740 HYPERLINK https:/www.MedChemE/740-y-p-tfa.html HYPERLINK https:/www.MedChemE/740-y-p-tfa.html Y-P HYPERLINK https:/www.MedChemE/740-y-p-tfa.html HYPERLINK https:/w

19、ww.MedChemE/740-y-p-tfa.html TFA(740YPDGFR; PDGFR 740Y-P) Cat. No.: HY-P0175 (740YPDGFR TFA; PDGFR 740Y-P TFA) Cat. No.: HY-P0175A740 Y-P (740YPDGFR; PDGFR 740Y-P) is a potent andcell-permeable PI3K activator. 740 Y-P readilybinds GST fusion proteins containing both the N-and C- terminal SH2 domains

20、 of p85 but fails tobind GST alone.740 Y-P TFA is a potent and cell-permeable PI3Kactivator. 740 Y-P TFA readily binds GST fusionproteins containing both the N- and C- terminalSH2 domains of p85 but fails to bind GST alone.Purity: 99.67%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 9

21、8%Clinical Data: No Development ReportedSize: 1 mg, 5 mgwww.MedChemE 3 HYPERLINK https:/www.MedChemE/A66.html A66Cat. No.: HY-13261 HYPERLINK https:/www.MedChemE/Acalisib.html Acalisib(GS-9820; CAL-120) Cat. No.: HY-12644A66 is a highly specific and selective p110inhibitor with an IC of 32 nM.50Acal

22、isib is a potent and selective PI3K inhibitorwith an IC of 12.7 nM.50Purity: 99.68%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.98%Clinical Data: Phase 1Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/act001.html ACT001Cat. N

23、o.: HY-128861A HYPERLINK https:/www.MedChemE/BYL-719.html Alpelisib(BYL-719) Cat. No.: HY-15244ACT001 is an orally active PAI-1 inhibitor byinhibiting the phosphorylation of PI3K and AKT.ACT001 inhibits the phosphorylation of STAT3 andPD-L1 expression by directly binding to STAT3.Alpelisib (BYL-719)

24、 is a potent, selective, andorally active PI3K inhibitor. Alpelisib (BYL-719)shows efficacy in targeting PIK3CA-mutated cancer.Alpelisib (BYL-719) also inhibitsp110/p110/p110/p110 with IC s of505/250/290/1200 nM, respectively.Purity: 99.62%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg

25、, 10 mg, 25 mg, 50 mgPurity: 99.95%Clinical Data: LaunchedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mg HYPERLINK https:/www.MedChemE/alpelisib-hydrochloride.html Alpelisib HYPERLINK https:/www.MedChemE/alpelisib-hydrochloride.html HYPERLINK https:/www.MedChemE/alpelisib-hydrochloride.html hy

26、drochloride(BYL-719 hydrochloride) Cat. No.: HY-15244A HYPERLINK https:/www.MedChemE/amdizalisib.html Amdizalisib(HMPL-689) Cat. No.: HY-132807Alpelisib hydrochloride (BYL-719 hydrochloride) isa potent, orally active, and selective PI3Kinhibitor with IC s of 5 nM, 250 nM, 290 nM and501200 nM for p11

27、0, p110, p110, and p110,respectively. Alpelisib hydrochloride (BYL-719hydrochloride) shows antineoplastic activity.Amdizalisib (HMPL-689) is a PI3K inhibitor and usedfor the research of inflammatory disease,autoimmune disease or cancer.Purity: 98%Clinical Data: LaunchedSize: 1 mg, 5 mgPurity: 98%Cli

28、nical Data: No Development ReportedSize: 1 mg, 5 mg HYPERLINK https:/www.MedChemE/amg-511.html AMG HYPERLINK https:/www.MedChemE/amg-511.html HYPERLINK https:/www.MedChemE/amg-511.html 511 HYPERLINK https:/www.MedChemE/amg-511.html HYPERLINK https:/www.MedChemE/AMG319.html AMG319Cat. No.: HY-13440 C

29、at. No.: HY-12948AMG 511 is a potent and orally available paninhibitor of class I PI3Ks, with Ks of 4 nM, 6 nM,i2 nM and 1 nM for PI3K, , and , respectively.AMG 511 significantly suppresses PI3K signalingthat is indicated by p-Akt (Ser473) decrease.AMG319 is a potent and selective PI3K kinaseinhibit

30、or with IC of 18 nM.50Purity: 98.81%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mgPurity: 98.27%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/gdc-0980.html Apitolisib HYPERLINK https:/www.MedChemE/gdc-0980.html HYP

31、ERLINK https:/www.MedChemE/aqx-016a.html AQX-016A(GDC-0980; GNE 390; RG 7422) Cat. No.: HY-13246Cat. No.: HY-115620Apitolisib (GDC-0980; GNE 390; RG 7422) is aselective, potent, orally bioavailable Class I PI3kinase and mTOR kinase (TORC1/2) inhibitorwith IC s of 5 nM/27 nM/7 nM/14 nM for50PI3K/PI3K

32、/PI3K/PI3K, and with a K ofi17 nM for mTOR.AQX-016A is an orally active and potent SHIP1agonist. AQX-016A can activate recombinant SHIP1enzyme in vitro and stimulate SHIP1 activity.AQX-016A also can inhibit the PI3K pathway and TNFaproduction, can be useful for various inflammatorydiseases research.

33、Purity: 98.26%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mgPurity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mg4 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK https:/www.MedChemE/arnicolide-d.html Arnicolide HYPERLINK https:/www.MedChemE/arnicol

34、ide-d.html HYPERLINK https:/www.MedChemE/arnicolide-d.html D HYPERLINK https:/www.MedChemE/arnicolide-d.html HYPERLINK https:/www.MedChemE/as-041164.html AS-041164Cat. No.: HY-N6843 Cat. No.: HY-118521Arnicolide D is a sesquiterpene lactone isolatedfrom Centipeda minima. Arnicolide D modulatesthe ce

35、ll cycle, activates the caspase signalingpathway and inhibits the PI3K/AKT/mTOR andSTAT3 signaling pathways.AS-041164 is a potent, selective and orally activePI3K isoform inhibitor with an IC of 70 nM.50AS-041164 shows less activity against PI3K,PI3K, and PI3K (IC s of 240 nM, 1.45 M, and501.70 M, r

36、espectively). AS-041164 hasanti-inflammatory effects.Purity: 99.20%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.32%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/AS-252424.html AS-252424 HYPERLINK https:/www

37、.MedChemE/AS-252424.html HYPERLINK https:/www.MedChemE/as-604850.html AS-604850Cat. No.: HY-13532 Cat. No.: HY-13531AS-252424 is a potent and selective PI3K inhibitorwith an IC of 3010 nM.50AS-604850 is a potent, selective andATP-competitive PI3K inhibitor with an IC value50of 0.25 M and a K value o

38、f 0.18 M. AS-604850ishows isoform selective inhibitor of PI3K withover 30-fold selectivity for PI3K and , and18-fold selectivity over PI3K, respectively.Purity: 99.31%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mgPurity: 99.91%Clinical Data: No Development ReportedSize: 10 mM 1

39、mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/AS-605240.html AS-605240 HYPERLINK https:/www.MedChemE/AS-605240.html HYPERLINK https:/www.MedChemE/Autophinib.html AutophinibCat. No.: HY-10109 Cat. No.: HY-101920AS-605240 is a specific and orally activeinhibitor of the PI3K, with

40、 an IC of 8 nM, and a50K of 7.8 nM.iPurity: 99.17%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 10 mg, 50 mg, 100 mgAutophinib is a potent, selective autophagyinhibitor with IC s of 90 nM and 40 nM for50starvation- and Rapamycin-induced autophagy,respectively. Autophinib is also an ATPcomp

41、etitive Vacuolar Protein Sorting 34 (VPS34)inhibitor with an IC of 19 nM.50Purity: 99.56%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 2 mg, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/az2.html AZ2 HYPERLINK https:/www.MedChemE/az2.html HYPERLINK https:/www.MedChemE/AZD-6482.h

42、tml AZD HYPERLINK https:/www.MedChemE/AZD-6482.html HYPERLINK https:/www.MedChemE/AZD-6482.html 6482Cat. No.: HY-111570(KIN-193) Cat. No.: HY-10344AZ2 is a highly selective PI3K inhibitor (ThepIC50 value for PI3K is 9.3). AZ2 can be used forthe research of inflammatory and immune diseases.AZD 6482 (

43、KIN-193) is a potent and selectivep110 inhibitor with an IC of 0.69 nM.50Purity: 99.38%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 25 mg, 50 mg, 100 mgPurity: 99.56%Clinical Data: Phase 1Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/AZD-8835.html

44、 AZD-8835 HYPERLINK https:/www.MedChemE/AZD-8835.html HYPERLINK https:/www.MedChemE/PI3K_gamma_inhibitor_3.html AZD3458Cat. No.: HY-12869 Cat. No.: HY-112443AZD8835 is a potent and selective inhibitor ofPI3K and PI3K with IC s of 6.2 and 5.7 nM,50respectively.AZD3458 is a potent and remarkably selec

45、tive PI3Kinhibitor with pIC s of 9.1, 5.1, 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.97%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/bay1082439.html BAY1082439Cat. No.: HY-100886 HYPERLINK https:/www.MedChemE/PI3K_alpha_-i

46、nhibitor-1.html BEBT-908(PI3K inhibitor 1) Cat. No.: HY-19763BAY1082439 is an orally bioavailable, selectivePI3K/ inhibitor. BAY1082439 also inhibitsmutated forms of PIK3CA. BAY1082439 is highlyeffective in inhibiting Pten-null prostate cancergrowth.BEBT-908 (PI3K inhibitor 1) is a selective PI3Kinh

47、ibitor extracted from patent US/20120088764A1,Compound 243, has an IC 98%Clinical Data: Phase 2Size: 1 mg, 5 mgPurity: 99.73%Clinical Data: Phase 2Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/PQR309.html Bimiralisib HYPERLINK https:/www.MedChemE/PQR309.html HYPERLINK ht

48、tps:/www.MedChemE/Brevianamide-F.html Brevianamide HYPERLINK https:/www.MedChemE/Brevianamide-F.html HYPERLINK https:/www.MedChemE/Brevianamide-F.html F(PQR309) Cat. No.: HY-12868 (Cyclo(L-Pro-L-Trp) Cat. No.: HY-100385Bimiralisib (PQR309) is a potent, brain-penetrant,orally bioavailable, pan-class

49、I PI3K/mTORinhibitor with IC s of 33 nM, 451 nM, 661 nM, 70850nM and 89 nM for PI3K, PI3K, PI3K, PI3K andmTOR, respectively. Bimiralisib is an mTORC1and mTORC2 inhibitor.Brevianamide F (Cyclo(L-Pro-L-Trp) is a mycotoxinisolated from Colletotrichum gloeosporioides,with antibacterial activity. Brevian

50、amide F showspotent PI3K inhibitory activity with an IC of504.8 M.Purity: 98.74%Clinical Data: Phase 2Size: 10 mM 1 mL, 2 mg, 5 mg, 10 mg, 50 mg, 100 mgPurity: 99.30%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/NVP-BKM120.html Bupar

51、lisib HYPERLINK https:/www.MedChemE/NVP-BKM120.html HYPERLINK https:/www.MedChemE/NVP-BKM120-Hydrochloride.html Buparlisib HYPERLINK https:/www.MedChemE/NVP-BKM120-Hydrochloride.html HYPERLINK https:/www.MedChemE/NVP-BKM120-Hydrochloride.html Hydrochloride(BKM120; NVP-BKM120) Cat. No.: HY-70063 (BKM

52、120 Hydrochloride; NVP-BKM120 Hydrochloride) Cat. No.: HY-15180Buparlisib (BKM120; NVP-BKM120) is a pan-class IPI3K inhibitor, with IC s of 52, 166, 116 and 26250nM for p110, p110, p110 and p110,respectively.Buparlisib Hydrochloride (BKM120 Hydrochloride) isa pan-class I PI3K inhibitor, with IC of 5

53、250nM/166 nM/116 nM/262 nM forp110/p110/p110/p110, respectively.Purity: 99.90%Clinical Data: Phase 3Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg, 200 mgPurity: 99.79%Clinical Data: Phase 3Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg6 Tel: 609-228-6898 Fax: 609-228-5909 Email: salesMedChemE HYPERLINK

54、 https:/www.MedChemE/cal-130.html CAL-130 HYPERLINK https:/www.MedChemE/cal-130.html HYPERLINK https:/www.MedChemE/cal-130-hydrochloride.html CAL-130 HYPERLINK https:/www.MedChemE/cal-130-hydrochloride.html HYPERLINK https:/www.MedChemE/cal-130-hydrochloride.html HydrochlorideCat. No.: HY-16122A Cat

55、. No.: HY-16122BCAL-130 is a PI3K and PI3K inhibitor with IC s of501.3 and 6.1 nM, respectively.CAL-130 is a PI3K and PI3K inhibitor with IC s of501.3 and 6.1 nM, respectively.Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.88%Clinical Data: No Development ReportedSize: 1

56、0 mM 1 mL, 5 mg, 10 mg, 50 mg HYPERLINK https:/www.MedChemE/cal-130-racemate.html CAL-130 HYPERLINK https:/www.MedChemE/cal-130-racemate.html HYPERLINK https:/www.MedChemE/cal-130-racemate.html Racemate HYPERLINK https:/www.MedChemE/cal-130-racemate.html HYPERLINK https:/www.MedChemE/CAY10505.html C

57、AY10505Cat. No.: HY-16122 Cat. No.: HY-13530CAL-130 Racemate is the racemate of CAL-130.CAL-130 Racemate is a PI3K inhibitor.CAY10505 is a potent and selective PI3K inhibitorwith an IC of 30 nM in neurons.50Purity: 98%Clinical Data: No Development ReportedSize: 1 mg, 5 mgPurity: 99.75%Clinical Data:

58、 No Development ReportedSize: 10 mM 1 mL, 10 mg, 25 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/cgs-15943.html CGS HYPERLINK https:/www.MedChemE/cgs-15943.html HYPERLINK https:/www.MedChemE/cgs-15943.html 15943 HYPERLINK https:/www.MedChemE/cgs-15943.html HYPERLINK https:/www.MedChemE/ch5132799.

59、html CH5132799Cat. No.: HY-100678 Cat. No.: HY-15466CGS 15943 is an orally bioavailable non-xanthineAdenosine Receptor antagonist. Its K for humaniA1, A2A, A2B, and A3 Adenosine Receptors are 3.5,4.2, 16, and 50 nM in transfected CHO cells,respectively.CH5132799 is a selective class I PI3K inhibitor

60、.CH5132799 inhibits class I PI3Ks, particularlyPI3K, with an IC of 14 nM.50Purity: 99.63%Clinical Data: No Development ReportedSize: 10 mM 1 mL, 1 mgPurity: 98.81%Clinical Data: Phase 1Size: 10 mM 1 mL, 5 mg, 10 mg, 50 mg, 100 mg HYPERLINK https:/www.MedChemE/chaetominine.html Chaetominine HYPERLINK