ライフサイエンスコーパス: FXIa

1 FXIa also cleaved CFH that was present on endothelial ce

2 FXIa and its isolated light chain (FXIa-LC) cleave S-236

3 FXIa binds to heparin (Kd approximately 0.7 x 10(-9) M)

4 FXIa contains four apple domains (A1-A4) and a catalytic

5 FXIa reduced the capacity of CFH to enhance the cleavage

6 FXIa(G193E) activated FIX with approximately 300-fold re

7 FXIa(G193E) inhibition by diisopropyl fluoro-phosphate w

8 FXIa-PN1 complexes are shown to be internalized and degr

9 n of milvexian (BMS-986177/JNJ-70033093, 17, FXIa K(i) = 0.11 nM) as a clinical candidate for the pre

10 Factor XIa and 1/2-FXIa activate the substrate factor IX, with similar kine

11 gh an intermediate with one active site (1/2-FXIa).

12 intermediate formation was detected with 1/2-FXIa, factor XIa with one inhibited active site, or a re

13 ery of a potent FXIa clinical candidate, 55 (FXIa Ki = 0.7 nM), with excellent preclinical efficacy i

14 Ia series, exemplified by compound 16, had a FXIa Ki = 0.16 nM with potent anticoagulant activity in

15 sed to block FXIIa-dependent FXI activation, FXIa-dependent factor IX (FIX) activation, or platelet-d

16 In addition, FXIa can activate factor FXII, which could contribute to

17 t SPGG's sulfation level moderately affected FXIa inhibition potency and selectivity over thrombin an

18 itor 6 displayed a potency of 551 nM against FXIa, which was at least 200-fold more selective than ot

19 ate that exhibits equivalent potency against FXIa.

20 izing p-aminobenzamidine, was intact for all FXIa mutants.

21 ected to open up a major route to allosteric FXIa anticoagulants with clinical relevance.

22 n FXIa/S557A but not in FXIa/C362S/C482S and FXIa/S557A/C362S/C482S.

23 57A, FXIa-HC, FXIa-LC, FXIa/C362S/C482S, and FXIa/S557A/C362S/C482S.

24 via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa.

25 xhibited near normal reactivity with FXa and FXIa in the absence of cofactors and in the presence of

26 nonclinical, and clinical studies of FXI and FXIa inhibitors.

27 itiated that compare drugs targeting FXI and FXIa to standard treatments or placebo.

28 , we examined binding of factor XI (FXI) and FXIa to heparin.

29 lusion, the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility

30 The concentrations of kallikrein and FXIa to cleave 50% (EC(50)) of (125)I-labeled pro-HGF du

31 tely resistant to cleavage by kallikrein and FXIa.

32 inhibitory complexes formed between PN1 and FXIa are stable when subjected to reducing agents, SDS,

33 e 309 by coagulation proteases (thrombin and FXIa), resulting in generation of a truncated form of FX

34 able rates of carbamylation for FXIa(WT) and FXIa(G193E), suggesting that the occupied active site ha

35 hrombin flux after 500 s was blocked by anti-FXIa antibody (O1A6), consistent with thrombin-feedback

36 sec in the simulation, consistent with anti-FXIa experiments.

37 of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors.

38 h literature-inspired pyridine N-oxide-based FXIa inhibitor 1, the imidazole linker was first replace

39 vestigate the molecular interactions between FXIa and the small synthetic substrate (S-2366), the mac

40 Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two

41 es the activation of factor IX by cell bound FXIa.

42 a-LC) cleave S-2366 at comparable rates, but FXIa-LC is a very poor activator of FIX, possibly becaus

43 PAB inhibited the hydrolysis of S-2366 by FXIa-LC in a classically competitive fashion.

44 nionic surface but not for FIX activation by FXIa in solution.

45 eavage products resulting from activation by FXIa or FXIa-LC.

46 e rate of factor IXa generation catalyzed by FXIa was unaffected by the presence of surfaces; however

47 potentiation in the rate of FIX cleavage by FXIa-LC.

48 into the mechanisms of activation of FIX by FXIa, we have investigated the kinetic properties of FXI

49 ented the cleavage of VE-cadherin induced by FXIa.

50 as FXIa/S557A inhibited FIX activation of by FXIa, FXIa-HC did not.

51 ysis of a sensitive fluorogenic substrate by FXIa in the presence of PN-2 to ascertain the kinetic ra

52 FXIa and its isolated light chain (FXIa-LC) cleave S-2366 at comparable rates, but FXIa-LC

53 the kinetic properties of FXIa-light chain (FXIa-LC) with its active site occupied by either a rever

54 2 enzymes of the contact activation complex, FXIa and FXIIa, play critical roles in the development o

55 Specific and saturable zinc-dependent FXIa binding was demonstrated to 250 +/- 48 sites per ac

56 in identification of compound 4 with desired FXIa inhibitory potency and good oral bioavailability bu

57 activated FIX similarly to wild-type dimeric FXIa.

58 de via PEGylation and demonstrated effective FXIa inhibition over extended periods in vivo.

59 Comparison of the kinetics of either FXIa- or PKa-induced activation of FIX suggest that PKa

60 the concentration of NaCl required to elute FXIa from heparin-Sepharose.

61 Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating facto

62 When converted to the active enzyme, FXIa, all the monomeric mutants activated FIX similarly

63 bed targeting the active form of the enzyme, FXIa.

64 ted in comparable rates of carbamylation for FXIa(WT) and FXIa(G193E), suggesting that the occupied a

65 tive serine proteases, was 4-fold faster for FXIa(G193E).

66 d peptide substrate, the K(assoc) of PN1 for FXIa was determined to be 7.9 x 10(4) m(-)(1) s(-)(1) in

67 e (S1 site probe) was 6-fold weaker than for FXIa(WT).

68 mechanism by which FXI or its activated form FXIa disrupts endothelial barrier function is unknown.

69 red its activity to wild type-activated FXI (FXIa(WT)).

70 t has also been reported that activated FXI (FXIa) binds to 1.5 x 10(6) sites per HUVEC and promotes

71 tivation; and inactivation of activated FXI (FXIa) by serine protease inhibitors.

72 ctively and potently inhibits activated FXI (FXIa) in human and animal blood.

73 The primary substrate of activated FXI (FXIa) is FIX, leading to FX activation (FXa) and thrombi

74 er FXI or its activated form, activated FXI (FXIa), directly interacts with the complement system.

75 iring factor IX activation by activated FXI (FXIa).

76 physiologic site for reactions involving FXI/FXIa.

77 of prekallikrein (PK) or factor XI/XIa (FXI/FXIa) binding to endothelial cells (HUVECs).

78 Factor XI/XIa (FXI/FXIa) represents a potential target for improved precisi

79 ng to an exosite on the heavy chain of FXIa (FXIa-HC) required for optimal cleavage rates of the two

80 a/S557A inhibited FIX activation of by FXIa, FXIa-HC did not.

81 g complexes of contact system enzymes FXIIa, FXIa, and kallikrein with antithrombin or C1 inhibitor,

82 moted the cleavage of FXI and PK to generate FXIa and plasma kallikrein, respectively.

83 examined FIX binding to FXIa/S557A, FXIa-HC, FXIa-LC, FXIa/C362S/C482S, and FXIa/S557A/C362S/C482S.

84 (6) as a highly selective inhibitor of human FXIa.

85 mportance, Arg15, Phe34, Pro13, and Arg20 in FXIa inhibition by PN2KPI.

86 n conclusion, enzyme activity is impaired in FXIa when Gly193 is replaced by a non-Gly residue, and r

87 avy and light chains are disulfide-linked in FXIa/S557A but not in FXIa/C362S/C482S and FXIa/S557A/C3

88 re disulfide-linked in FXIa/S557A but not in FXIa/C362S/C482S and FXIa/S557A/C362S/C482S.

89 other SERPIN known to significantly inhibit FXIa.

90 completely abolished its ability to inhibit FXIa.

91 C38 were tested for their ability to inhibit FXIa.

92 Zn2+ augments the ability of PN-2 to inhibit FXIa.

93 uman and murine plasma, and PN2KPI inhibited FXIa activity in both human and murine plasma in vitro.

94 smooth muscle cells was active in inhibiting FXIa.

95 Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such p

96 ets and in plasma of pregnant women inhibits FXIa and tissue-type plasminogen activator-induced clot

97 with a saturating concentration of isolated FXIa-HC did not result in any potentiation in the rate o

98 yme-substrate interaction, then the isolated FXIa-HC should inhibit the rate of FIX activation by dep

99 FIX binding to FXIa/S557A, FXIa-HC, FXIa-LC, FXIa/C362S/C482S, and FXIa/S557A/C362S/C482S.

100 ally bioavailable pyridine-based macrocyclic FXIa inhibitors.

101 e discovery of a novel series of macrocyclic FXIa inhibitors containing a pyrazole P2' moiety.

102 A novel series of macrocyclic FXIa inhibitors was designed based on our lead acyclic p

103 The macrocyclic FXIa series, exemplified by compound 16, had a FXIa Ki =

104 e doses of milvexian, an oral small-molecule FXIa inhibitor, in healthy Japanese participants.

105 Moreover, FXIa reduced the cleavage of C3b by factor I in serum.

106 crocycles, which were double-digit nanomolar FXIa inhibitors, were further optimized with assistance

107 ome of these inhibitors showed low nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity

108 Thrombin-feedback activation of FXIa became prominent and reached 5 pM FXIa at >500 sec

109 e able to regulate the catalytic activity of FXIa and plasma kallikrein, respectively, despite the in

110 Addition of FXIa to plasma was able to reverse the ability of TFPI t

111 ntration-dependent decrease in the amount of FXIa bound to HUVEC.

112 Therefore, the binding of FXIa to activated platelets was compared with FXIa bindi

113 The binding of FXIa with plasminogen activator inhibitor 1 and very low

114 chain polyphosphate enhanced the capacity of FXIa to cleave CFH.

115 binding to an exosite on the heavy chain of FXIa (FXIa-HC) required for optimal cleavage rates of th

116 vy chain and the other on the light chain of FXIa is required to mediate the formation of the Michael

117 absence of either Ca2+ or the heavy chain of FXIa there was substantial accumulation of the inactive

118 essential for the structure-based design of FXIa-selective inhibitors.

119 the complex between the catalytic domain of FXIa and the Kunitz protease inhibitor (KPI) domain of a

120 The effect of FXIa on barrier function may be another way by which FXI

121 CHWA-D Abeta caused a >5-fold enhancement of FXIa inhibition by PN-2/AbetaPP.

122 f FIX binding via the heavy chain exosite of FXIa determines the affinity of the enzyme-substrate int

123 The generation of FXIa in plasma induced the cleavage of CFH.

124 ction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interacti

125 esidues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition poten

126 odeling also indicates that the inability of FXIa(G193E) to bind antithrombin/APPI or activate FIX is

127 ation and Zn2+ increases the inactivation of FXIa.

128 undexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibitio

129 n and are required for optimal inhibition of FXIa and FXa.

130 Inhibition of FXIa by ATIII in the presence of heparin was decreased 4

131 c rate constants governing the inhibition of FXIa by PN-2.

132 exert opposite effects on the inhibition of FXIa by PN-2.

133 Inhibition of FXIa by PN2 requires interactions between the two protei

134 Thus, inhibition of FXIa by PN2KPI is a promising approach to antithrombotic

135 mined the effect of heparin on inhibition of FXIa by the inhibitors C1-inhibitor (C1-INH) and antithr

136 fect was also observed for the inhibition of FXIa by ZPI mutants.

137 evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while prese

138 pound 16b, a potent, reversible inhibitor of FXIa (Ki = 0.3 nM) having in vivo antithrombotic efficac

139 l models and human genetics, an inhibitor of FXIa has the potential to be an antithrombotic agent wit

140 (-)(1), making PN1 a far better inhibitor of FXIa than C1 inhibitor, which is the only other SERPIN k

141 2) is a potent, highly specific inhibitor of FXIa, suggesting its possible role in the inhibition of

142 and a physiologically important inhibitor of FXIa.

143 highly selective small molecule inhibitor of FXIa.

144 Novel inhibitors of FXIa containing an (S)-2-phenyl-1-(4-phenyl-1H-imidazol-

145 Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy

146 tent, selective peptidomimetic inhibitors of FXIa were designed and synthesized.

147 efforts at identifying potent inhibitors of FXIa with a focus on discovering an acute antithrombotic

148 XIa activity, including direct inhibitors of FXIa, have demonstrated good antithrombotic efficacy wit

149 ctive, and orally bioavailable inhibitors of FXIa.

150 hanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FX

151 tanding of substrate binding interactions of FXIa, the structural information essential for the struc

152 the release of PN-2, limits the lifetime of FXIa activity within the locus of activated platelets.

153 ch predominates and prolongs the lifetime of FXIa after platelet activation.

154 Inhibitor 6 reduced V(MAX) of FXIa hydrolysis of chromogenic substrate without affecti

155 We conducted sensitive measurements of FXIa activity in the presence of human platelets before

156 ctions in the S1, S1beta, and S1' pockets of FXIa through a combination of structure-based drug desig

157 To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of pote

158 have investigated the kinetic properties of FXIa-light chain (FXIa-LC) with its active site occupied

159 Partial reduction of FXIa/S557A to produce heavy and light chains resulted in

160 We investigated the role of FXIa in human umbilical vein endothelial cell (HUVEC) or

161 results suggest that the hemostatic role of FXIa may be attributed not only to activation of FIX but

162 indicate that the unoccupied active site of FXIa(G193E) is incompletely formed, and the amide N of G

163 ue structural features in the active site of FXIa.

164 conformational changes in the active site of FXIa.

165 that 6 bound in the heparin-binding site of FXIa.

166 To determine the structure of FXIa, we derived a recombinant catalytic domain of FXI,

167 with kinetic parameters similar to those of FXIa.

168 Factor XI (FXI) is the zymogen of FXIa, which cleaves FIX in the intrinsic pathway of coag

169 molecular weight kininogen had no effect on FXIa binding to platelets, but revealed a concentration-

170 Similar stimulatory effects on FXIa inhibition by PN-2/AbetaPP were also observed with

171 of compound 23 with subnanomolar potency on FXIa, enhanced selectivity over other coagulation protea

172 e than one anion-binding, allosteric site on FXIa.

173 ylglucopyranosyl scaffold may be the optimal FXIa inhibitor for further preclinical studies.

174 (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa.

175 Patients with heart disease on FXI or FXIa inhibitors experienced less bleeding than patients

176 n phase 2 studies, drugs that inhibit FXI or FXIa prevent venous thromboembolism after total knee art

177 K preferentially bound to HUVECs over FXI or FXIa.

178 roducts resulting from activation by FXIa or FXIa-LC.

179 tic activation of FXI by FXIIa, thrombin, or FXIa either in solution or on an anionic surface but not

180 trations, PK (450 nM) abolished FITC-FXI or -FXIa binding to HUVEC suspensions in the absence or pres

181 ons without added Zn2+, whereas FITC-FXI or -FXIa binding to HUVEC suspensions required 10 microM add

182 the absence of HK, the level of FITC-FXI or -FXIa binding was half that seen in its presence.

183 ormal substrate binding compared with plasma FXIa; however, all except E98A and K192A had impaired va

184 on of FXIa became prominent and reached 5 pM FXIa at >500 sec in the simulation, consistent with anti

185 Herein we describe the discovery of a potent FXIa clinical candidate, 55 (FXIa Ki = 0.7 nM), with exc

186 As a result, a potent FXIa inhibitor 3f (K(i) = 0.17 nM) was discovered.

187 ed to the discovery of compound 6f, a potent FXIa inhibitor with selectivity against most of the rele

188 in the FXIa active site, resulting in potent FXIa inhibitors.

189 The discovery of potent FXIa inhibitors with good oral bioavailability has been

190 Predictably, FXIa activation of FIX(PCEGF1) was normal, whereas it wa

191 the reported FXIa Glu193 mutant, we prepared FXIa with Asp (short side chain) or Lys (opposite charge

192 nly the activated platelet surface protected FXIa from inhibition by protease nexin 2.

193 As in the purified system, HK protects FXIa from inactivation and Zn2+ increases the inactivati

194 HK protects FXIa from inactivation in a dose dependent and saturable

195 193E), we expressed and purified recombinant FXIa(G193E), activated it to FXIa(G193E), and compared i

196 dies using a variety of approaches to reduce FXIa activity, including direct inhibitors of FXIa, have

197 r (KPI) domain of a physiologically relevant FXIa inhibitor, protease nexin 2 (PN2).

198 th venous and arterial thrombosis, rendering FXIa a potential target for the development of antithrom

199 For comparison to the reported FXIa Glu193 mutant, we prepared FXIa with Asp (short sid

200 identify an orally bioavailable, reversible FXIa inhibitor.

201 fore, we examined FIX binding to FXIa/S557A, FXIa-HC, FXIa-LC, FXIa/C362S/C482S, and FXIa/S557A/C362S

202 The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has b

203 Since FXIa proteolytically modifies the amyloid precursor prot

204 Six FXIa catalytic domain residues (Glu(98), Tyr(143), Ile(1

205 To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a

206 the extrinsic pathway followed by late-stage FXIa contributions, with fibrin localizing thrombin via

207 ctor D inhibitor and exhibited submicromolar FXIa activity and an encouraging absorption, distributio

208 s emerges as a novel anticoagulant targeting FXIa under conditions in which the coagulation activatio

209 We demonstrate that FXIa increases endothelial cell permeability by inducing

210 We found that FXIa neutralized both endothelium- and platelet-derived

211 We found that FXIa neutralized CFH by cleavage of the R341/R342 bonds.

212 These results imply that FXIa is the primary in vivo target for Desmolaris at ant

213 These results suggest that FXIa generation enhances the activity of the complement

214 activation of FXI in plasma and suggest that FXIa may provide a link between tissue factor-initiated

215 The FXIa inhibitor asundexian at doses of 20 mg and 50 mg on

216 f crystal structures for zymogen FXI and the FXIa catalytic domain have enhanced our understanding of

217 e conclude that substrate recognition by the FXIa exosite(s) requires disulfide-linked heavy and ligh

218 This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small

219 rogen bond with the carbonyl of Leu41 in the FXIa active site, resulting in potent FXIa inhibitors.

220 d metalloproteinase 10 (ADAM10) mediates the FXIa-dependent cleavage of VE-cadherin, because adding a

221 ed extensive pharmacologic evaluation of the FXIa mechanism up to the ID90 for thrombus inhibition.

222 Occupancy of the active site of the FXIa-LC by S-2366 also resulted in noncompetitive inhibi

223 alysis of the X-ray crystal structure of the FXIa/11h complex.

224 resence of an exosite for FIX binding on the FXIa-LC remote from its active site.

225 from P5 to P2' in ecotin was mutated to the FXIa substrate sequence, and the structures of the rhFXI

226 a-branching causes steric conflicts with the FXIa 140-loop, which could perturb the local tertiary st

227 toward macromolecular interactions with the FXIa mutants.

228 Therefore, FXIa is a potential target for anti-thrombosis therapy.

229 Thus FXIa, generated on contact phase activation, cleaves che

230 Mz-IIa catalyze factor (F) XI activation to FXIa, which sustains alpha-thrombin production through a

231 or protein Kunitz domain inhibitor (APPI) to FXIa(G193E) was impaired approximately 8000- and approxi

232 FXI undergoes autoactivation to FXIa in the presence of heparin.

233 Therefore, we examined FIX binding to FXIa/S557A, FXIa-HC, FXIa-LC, FXIa/C362S/C482S, and FXIa

234 ucture of tetrahydroquinoline 3 complexed to FXIa.

235 ied recombinant FXIa(G193E), activated it to FXIa(G193E), and compared its activity to wild type-acti

236 In this phase 2b trial, FXIa inhibition with asundexian did not reduce the compo

237 Wild type FXIa eluted from the column at 320 mM NaCl, whereas FXIa

238 sing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation.

239 However, whereas FXIa/S557A inhibited FIX activation of by FXIa, FXIa-HC

240 uted from the column at 320 mM NaCl, whereas FXIa with multiple substitutions (A252-254 or A250-255)

241 barrier function may be another way by which FXIa contributes to the development of inflammatory dise

242 This study reveals a novel pathway by which FXIa regulates vascular permeability.

243 ovel model for factor IX activation in which FXIa binds to activated platelets by one chain of the di

244 Treatment of cultured endothelial cells with FXIa increased the generation of FXa and promoted TF-dep

245 s was also reduced after incubating CFH with FXIa.

246 XIa to activated platelets was compared with FXIa binding to HUVEC and HEK293 cells immobilized on mi

247 ly elevated stoichiometry of inhibition with FXIa in the absence of heparin.

248 strates its unique binding interactions with FXIa.

249 portant interactions of the lead series with FXIa while simultaneously seeking to improve metabolic s

250 nce heparin potentiates activated factor XI (FXIa) inhibition by protease nexin-2 by providing a temp

251 Milvexian, an oral activated Factor XI (FXIa) inhibitor, is in clinical studies where it may be

252 Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with

253 Activated coagulation factor XI (FXIa) is a highly attractive antithrombotic target as it

254 Activated Factor XI (FXIa) is a key enzyme in the amplification phase of the

255 ZPI) inhibition of factors Xa (FXa) and XIa (FXIa) by a template mechanism.

256 sic pathway of blood coagulation factor XIa (FXIa) activates factor IX (FIX) by cleaving the zymogen

257 r XI (FXI) and its protease form factor XIa (FXIa) as drug targets for treating and preventing thromb

258 Factor XIa (FXIa) cleaved chem163S, generating a novel chemerin form

259 Factor XIIa (FXIIa) and factor XIa (FXIa) contribute to thrombosis in animal models, whereas

260 ic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy

261 Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increa

262 l molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal ef

263 Factor XIa (FXIa) inhibitors are promising novel anticoagulants, whi

264 Oral factor XIa (FXIa) inhibitors may provide a promising new antithrombo

265 Factor XIa (FXIa) is a blood coagulation enzyme that is involved in

266 Inhibition of factor XIa (FXIa) is a novel paradigm for developing anticoagulants

267 Factor XIa (FXIa) is a serine protease important for initiating the

268 Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to

269 an exosite on the heavy chain of factor XIa (FXIa) is essential for the optimal activation of FIX.

270 o select residues in coagulation factor XIa (FXIa) potentially important for substrate and inhibitor

271 Human coagulation factor XIa (FXIa), a serine protease activated by site-specific clea

272 Moreover, the activity of factor XIa (FXIa), but not FXIIa, was higher in APP-KO mice compared

273 teases (such as Factor Xa (FXa), Factor XIa (FXIa), urokinase-type plasminogen activator (uPA), throm

274 g proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated q

275 t with Ala or Val in coagulation factor XIa (FXIa).

276 lasma kallikrein and coagulation factor XIa (FXIa).

277 potent inhibitor of coagulation factor XIa (FXIa).

278 hibitor of the blood coagulation Factor XIa (FXIa).

279 e inhibitor of blood coagulation factor XIa (FXIa).

280 G) as an allosteric inhibitor of factor XIa (FXIa).