NPASS Compound

Natural Product: NPC316629

Natural Product ID	NPC316629
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Epoprostenol
IUPAC Name	(5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid
Synonyms	Epoprostenol; Flolan; PG-I2; PGI2; PGX; Prostacyclin; Prostaglandin I2; Prostaglandin X; U-53217
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1139
PubChem CID	5282411
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000513] Eicosanoids [CHEMONTID:0000514] Prostaglandins and related compounds

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 57 58 0 0 0 0 0 0 0 0999 V2000 -7.7420 0.0068 -0.2349 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7366 0.6759 0.6753 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0148 1.8065 -0.0105 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2668 1.3527 -1.2251 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2418 0.3216 -0.8805 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2455 0.8515 0.0976 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2546 -0.2340 0.3872 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9732 0.0144 0.2433 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1261 -0.9202 0.4803 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3002 -2.3401 0.7762 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9479 -2.4886 1.9741 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0858 -3.0069 0.8061 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7772 -2.3582 -0.3523 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9756 -1.1630 -0.7753 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9073 -0.0201 -1.0003 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2417 -0.6223 -0.7475 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4115 -0.1504 -1.1457 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6997 -0.8166 -0.8493 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6065 0.0644 -0.0544 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8874 1.3354 -0.8486 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7866 2.1676 -0.0192 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0006 1.8997 0.0658 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2719 3.2534 0.6678 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0354 -1.7765 -0.0134 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6019 1.9838 -0.3585 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5401 0.7388 -0.4438 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2242 -0.3978 -1.1092 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1538 -0.8573 0.3615 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0049 -0.0585 1.0501 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2583 1.0523 1.5949 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3526 2.2700 0.7512 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7345 2.6276 -0.2868 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7618 2.2186 -1.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9416 0.9037 -1.9902 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6974 0.0040 -1.8059 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7471 -0.5587 -0.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7222 1.1288 1.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5682 -1.1979 0.7058 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6817 1.0255 -0.0896 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7942 -0.6023 1.3042 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8351 -2.8206 -0.0692 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8900 -1.6416 2.4797 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5311 -2.7285 1.7898 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9849 -4.0859 0.6808 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9730 -3.0811 -1.1485 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3207 -1.3927 -1.6166 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8163 0.3267 -2.0533 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7142 0.8398 -0.3219 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4066 0.7711 -1.7159 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1709 -1.0628 -1.8292 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4993 -1.7641 -0.2915 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5310 -0.4773 0.1723 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1004 0.3220 0.9009 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9672 1.8883 -1.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4178 1.0815 -1.7806 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8748 3.8170 1.2866 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4770 1.8744 -1.3527 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 16 24 1 0 6 25 1 0 14 9 1 0 24 13 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 0 2 30 1 0 3 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 5 35 1 0 5 36 1 0 6 37 1 1 7 38 1 0 8 39 1 0 9 40 1 1 10 41 1 6 11 42 1 0 12 43 1 0 12 44 1 0 13 45 1 6 14 46 1 6 15 47 1 0 15 48 1 0 17 49 1 0 18 50 1 0 18 51 1 0 19 52 1 0 19 53 1 0 20 54 1 0 20 55 1 0 23 56 1 0 25 57 1 0 M END

Standard InCHIKey	KAQKFAOMNZTLHT-OZUDYXHBSA-N
Standard InCHI	InChI=1S/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17+,18+,19-/m0/s1
SMILES	CCCCC[C@@H](/C=C/[C@H]1[C@H](O)C[C@H]2[C@@H]1C/C(=C/CCCC(=O)O)/O2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	352.22	Volume:	373.405 ? Van der Waals volume.
Dense:	0.943	LogP:	2.772 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.593 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.142 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	12.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.414	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.255	Fsp³:	0.75
MCE-18:	30.457 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.424	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.383	Promiscuous compounds:	0.754

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.42	MDCK Permeability:	-5.065
Pgp-inhibitor:	0.0	Pgp-substrate:	0.168
PAMPA:	0.995 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.052
20% Bioavailability (F20%):	0.826	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.058
Plasma Protein Binding (PPB):	93.425%	Volume Distribution (VD):	-0.513
Fu:	5.518% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.939
OATP1B3 inhibitor:	0.944	BCRP inhibitor:	0.003
BSEP inhibitor:	0.904

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.028	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.411	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.05	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.004	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.005
HLM stability:	0.007 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

7.969

Half-life (T1/2):

1.213

ADMET: Toxicity

hERG Blockers:	0.061	hERG Blockers (10um):	0.173
Human Hepatotoxicity (H-HT):	0.567	Drug-induced Liver Injury (DILI):	0.075
AMES Toxicity:	0.122	Rat Oral Acute Toxicity:	0.193
Maximum Recommended Daily Dose:	0.538	Skin Sensitization:	0.858
Carcinogencity:	0.293	Eye Corrosion:	0.354
Eye Irritation:	0.929	Respiratory Toxicity:	0.68
Drug-induced Neurotoxicity:	0.059	Ototoxicity:	0.768
Hematotoxicity:	0.293	Drug-induced Nephrotoxicity:	0.72
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.111	Hek293 Cytotoxicity:	0.071
BCF:	0.391 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.115 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.473 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.559 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1172/JCI16309]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1371/journal.pone.0115359]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[10557354]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11034610]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11419736]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[11530998]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1175644]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12391014]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12812989]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12840027]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[12878451]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15084647]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1521032]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15230696]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[15314235]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[16112079]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[16770722]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[1687010]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17116739]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17190852]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17875433]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18311922]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18544912]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[18799520]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[19425150]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[19961175]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20506249]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20601097]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	bile	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	faeces	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	urine	n.a.	PMID[20708442]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[20876113]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[21798258]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[2268561]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[22711758]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23315938]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23717534]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23752203]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23810710]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23811455]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23868375]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[23919613]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24101735]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24399466]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24494566]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24558969]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[24816727]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25114169]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25181601]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25293588]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[25644343]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[26236990]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[27471436]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[3179836]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[347637]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[4696527]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[5432584]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[6121420]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[6780563]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[8600370]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[8987136]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[9192820]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	PMID[9800648]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	Database[MetaboLights]
NPO20338	Mus musculus	Species	Muridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Potency	3
Inhibition	2
EC50	4
IC50	6
Composite Activity - Active	1
Composite Activity - Marginal	1
Alkaline Phosphatase Increase - Index Value	1
Alkaline Phosphatase Increase - Number of Reports	1
SGOT Increase - Index Value	1
SGOT Increase - Number of Reports	1
SGPT Increase - Index Value	1
SGPT Increase - Number of Reports	1
LDH Increase - Number of Reports	1
GGT Increase - Index Value	1
GGT Increase - Number of Reports	1
HepSE_bilirubinemia	1
HepSE_cholecystitis	1
HepSE_cholelithiasis	1
HepSE_cirrhosis	1
HepSE_hepatic failure	1
HepSE_hepatic necrosis	1
HepSE_hepatomegaly	1
HepSE_jaundice	2
HepSE_liver fatty	1
HepSE_liver function tests abnormal	1
HepSE_Combined Scores	1
Hit score	1
LDH Increase - Index Value	1
HepSE_liver disease	1
ED20	1
HepSE_elevated liver function tests	1
HepSE_hepatitis	1
Relative activity	1

Activity Type	# Activity
Organism	11
Individual protein	4
Others	3
Phenotype	27

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT94	Individual protein	Aldehyde dehydrogenase 1A1	Homo sapiens	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT698	Individual protein	Regulator of G-protein signaling 4	Homo sapiens	Potency	n.a.	67.0	nM	PubChem BioAssay data set
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	10.8	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	-8.72	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	15101.4	nM	PubChem BioAssay data set
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Hit score	=	0.02737	n.a.	DOI[10.1101/2020.04.21.054387]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	20000.0	nM	DOI[10.6019/CHEMBL4651402]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	IC50	>	19952.62	nM	DOI[10.6019/CHEMBL4651402]
NPT2	Others	Unspecified	n.a.	EC50	=	3.3	nM	PMID[6988588]
NPT2	Others	Unspecified	n.a.	EC50	=	28.0	nM	PMID[6988588]
NPT2	Others	Unspecified	n.a.	IC50	=	8000.0	nM	PMID[1404230]
NPT20596	Phenotype	Hepatotoxicity	n.a.	Composite Activity - Active	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	Composite Activity - Marginal	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	Alkaline Phosphatase Increase - Index Value	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	Alkaline Phosphatase Increase - Number of Reports	<	4.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	SGOT Increase - Index Value	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	SGOT Increase - Number of Reports	<	4.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	SGPT Increase - Index Value	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	SGPT Increase - Number of Reports	<	4.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	LDH Increase - Number of Reports	<	4.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	GGT Increase - Index Value	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	GGT Increase - Number of Reports	<	4.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_bilirubinemia	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cholecystitis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cholelithiasis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_cirrhosis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatic failure	=	1.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatic necrosis	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatomegaly	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_jaundice	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver fatty	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver function tests abnormal	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_Combined Scores	=	1.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	LDH Increase - Index Value	=	0.0	n.a.	PMID[16472241]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_liver disease	=	0.0	n.a.	PMID[22194678]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT605	Organism	Homo sapiens	Homo sapiens	EC50	=	0.00165	ug.mL-1	PMID[6854582]
NPT605	Organism	Homo sapiens	Homo sapiens	Relative activity	=	299394.0	n.a.	PMID[6854582]
NPT605	Organism	Homo sapiens	Homo sapiens	EC50	=	0.0174	ug.mL-1	PMID[6854582]
NPT605	Organism	Homo sapiens	Homo sapiens	IC50	=	0.66	nM	PMID[2419560]
NPT605	Organism	Homo sapiens	Homo sapiens	IC50	=	8.0	nM	PMID[7504734]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED20	=	0.00067	mg kg-1	PMID[6854582]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	IC50	=	2.6	nM	PMID[2419560]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_elevated liver function tests	=	0.0	n.a.	PMID[22194678]
NPT20596	Phenotype	Hepatotoxicity	n.a.	HepSE_hepatitis	=	0.0	n.a.	PMID[22194678]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC316629 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	22088
0.1-0.2	26686
0.2-0.3	966
0.3-0.4	90
0.4-0.5	21
0.5-0.6	6
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.5077	Remote Similarity	NPC260814
0.5077	Remote Similarity	NPC323249
0.5077	Remote Similarity	NPC27949
0.5077	Remote Similarity	NPC39547
0.5075	Remote Similarity	NPC115418
0.5075	Remote Similarity	NPC600545

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC316629 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5785
0.1-0.2	3233
0.2-0.3	100
0.3-0.4	23
0.4-0.5	4
0.5-0.6	2
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD4250	Phase 4
1.0	High Similarity	NPD4251	Approved
0.7759	Intermediate Similarity	NPD4249	Approved
0.5077	Remote Similarity	NPD4271	Phase 4
0.5075	Remote Similarity	NPD4252	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data