NPASS Compound

Natural Product: NPC109546

Natural Product ID	NPC109546
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7Alpha-Hydroxycholesterol
IUPAC Name	(3S,7S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL497207
PubChem CID	107722
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003566] Cholestane steroids [CHEMONTID:0001469] Cholesterols and derivatives

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 75 78 0 0 0 0 0 0 0 0999 V2000 -6.3905 0.7541 1.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3586 1.0200 -0.4643 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6354 2.3326 -0.7581 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9063 -0.0824 -1.3339 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5263 -0.6128 -1.1804 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1405 -1.1969 0.1191 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6945 -1.7472 0.0855 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5400 -2.8082 -0.9482 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7840 -0.5897 -0.0105 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0144 0.2909 1.2164 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6689 0.8931 1.5761 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1989 0.4800 0.4495 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6666 0.3663 0.7475 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3362 0.0316 -0.5689 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8095 -1.2642 -1.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3172 -1.3651 -1.1412 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3223 -0.9103 0.1457 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0105 -1.8884 1.2197 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8196 -0.0054 -0.4728 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3384 -1.4488 -0.4890 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4757 0.6714 -1.6819 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5548 1.6255 -1.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5262 1.1314 -0.2778 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8521 0.5319 0.9536 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3927 0.6703 0.7140 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6948 1.3958 1.5666 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2376 1.5866 1.3803 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9888 2.7522 0.6656 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5153 0.3051 -0.7728 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4493 -0.3377 1.1716 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3810 1.1299 1.4511 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5924 1.2659 1.5886 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4352 1.2446 -0.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2764 3.1459 -0.3603 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6072 2.4439 -1.8548 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6615 2.3939 -0.2684 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6801 -0.9159 -1.2108 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0862 0.2130 -2.4150 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3380 -1.2966 -2.0476 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8413 0.2679 -1.4242 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1396 -0.3866 0.9054 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8531 -1.9580 0.4590 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6246 -2.2654 1.0894 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8996 -3.6688 -0.5984 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2358 -2.4455 -1.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5566 -3.2791 -1.0911 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9165 -0.0641 -0.9538 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6806 1.1151 0.9049 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4596 -0.2661 2.0534 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7208 2.0166 1.5837 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3195 0.5966 2.5712 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0485 1.1306 -0.4262 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8721 -0.4866 1.4349 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0740 0.8237 -1.3308 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1584 -1.3378 -2.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2241 -2.1266 -0.5558 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1510 -0.8555 -2.0110 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0662 -2.4472 -1.2560 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0100 -1.4523 2.2400 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0144 -2.2921 1.0668 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6672 -2.7645 1.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0056 -1.9577 0.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4363 -1.4559 -0.5057 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0338 -1.9553 -1.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8640 -0.0493 -2.4019 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6743 1.2630 -2.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1492 1.8292 -2.2277 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1621 2.6284 -0.9938 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0711 2.0512 0.0933 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1321 -0.5133 1.1353 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1379 1.0802 1.8818 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1898 1.8659 2.4245 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7420 1.7170 2.3713 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3802 2.7679 -0.2270 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4145 0.6682 -0.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 1 14 19 1 0 19 20 1 1 19 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 23 29 1 0 17 9 1 0 25 19 1 0 17 12 1 0 27 13 1 0 1 30 1 0 1 31 1 0 1 32 1 0 2 33 1 0 3 34 1 0 3 35 1 0 3 36 1 0 4 37 1 0 4 38 1 0 5 39 1 0 5 40 1 0 6 41 1 0 6 42 1 0 7 43 1 1 8 44 1 0 8 45 1 0 8 46 1 0 9 47 1 6 10 48 1 0 10 49 1 0 11 50 1 0 11 51 1 0 12 52 1 6 13 53 1 1 14 54 1 6 15 55 1 0 15 56 1 0 16 57 1 0 16 58 1 0 18 59 1 0 18 60 1 0 18 61 1 0 20 62 1 0 20 63 1 0 20 64 1 0 21 65 1 0 21 66 1 0 22 67 1 0 22 68 1 0 23 69 1 1 24 70 1 0 24 71 1 0 26 72 1 0 27 73 1 1 28 74 1 0 29 75 1 0 M END

Standard InCHIKey	OYXZMSRRJOYLLO-RVOWOUOISA-N
Standard InCHI	InChI=1S/C27H46O2/c1-17(2)7-6-8-18(3)21-9-10-22-25-23(12-14-27(21,22)5)26(4)13-11-20(28)15-19(26)16-24(25)29/h16-18,20-25,28-29H,6-15H2,1-5H3/t18-,20+,21-,22+,23+,24-,25+,26+,27-/m1/s1
SMILES	CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@@]1(C)CC[C@@H](CC1=C[C@H]3O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	402.35	Volume:	456.266 ? Van der Waals volume.
Dense:	0.882	LogP:	5.967 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.643 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.656 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.525	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.41	Fsp³:	0.926
MCE-18:	69.577 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.905	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.327	Promiscuous compounds:	0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.454	MDCK Permeability:	-5.109
Pgp-inhibitor:	0.0	Pgp-substrate:	0.149
PAMPA:	0.042 ? 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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.318
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.156	MRP1:	0.027
Plasma Protein Binding (PPB):	86.506%	Volume Distribution (VD):	-0.341
Fu:	9.684% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.224
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.01
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.005
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.314
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.537 ? 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):

12.539

Half-life (T1/2):

0.753

ADMET: Toxicity

hERG Blockers:	0.144	hERG Blockers (10um):	0.399
Human Hepatotoxicity (H-HT):	0.613	Drug-induced Liver Injury (DILI):	0.295
AMES Toxicity:	0.479	Rat Oral Acute Toxicity:	0.164
Maximum Recommended Daily Dose:	0.535	Skin Sensitization:	0.979
Carcinogencity:	0.844	Eye Corrosion:	0.36
Eye Irritation:	0.975	Respiratory Toxicity:	0.798
Drug-induced Neurotoxicity:	0.041	Ototoxicity:	0.497
Hematotoxicity:	0.46	Drug-induced Nephrotoxicity:	0.431
Genotoxicity:	0.014	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.7	Hek293 Cytotoxicity:	0.431
BCF:	2.608 ? 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:	4.395 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.274 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.039 ? 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
Ki	2
%Max (Mean)	13
%Inhib (Mean)	13
EC50	1
IC50	5
Growth Rate	19

Activity Type	# Activity
Individual protein	20
Cell line	23
Single protein	9
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT103	Individual protein	Nuclear receptor ROR-gamma	Homo sapiens	Ki	=	10.0	nM	DOI[10.1039/C3MD00005B]
NPT1627	Individual protein	G-protein coupled receptor 35	Homo sapiens	%Max (Mean)	=	1.381	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT1109	Individual protein	Apelin receptor	Homo sapiens	%Max (Mean)	=	-1.529	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT1109	Individual protein	Apelin receptor	Homo sapiens	%Inhib (Mean)	=	-29.62	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT222	Individual protein	Alpha-2a adrenergic receptor	Homo sapiens	%Inhib (Mean)	=	-52.44	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	%Max (Mean)	=	-2.679	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT1627	Individual protein	G-protein coupled receptor 35	Homo sapiens	%Inhib (Mean)	=	-25.92	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT226	Individual protein	Beta-2 adrenergic receptor	Homo sapiens	%Inhib (Mean)	=	-36.69	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT226	Individual protein	Beta-2 adrenergic receptor	Homo sapiens	%Max (Mean)	=	-2.428	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT222	Individual protein	Alpha-2a adrenergic receptor	Homo sapiens	%Max (Mean)	=	-2.32	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	%Inhib (Mean)	=	-53.87	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT26694	Single protein	Lipoxin A4 receptor	Homo sapiens	%Inhib (Mean)	=	-23.96	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT30125	Single protein	C5a anaphylatoxin chemotactic receptor	Homo sapiens	%Inhib (Mean)	=	-25.22	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT26694	Single protein	Lipoxin A4 receptor	Homo sapiens	%Max (Mean)	=	-2.601	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT23767	Single protein	G-protein coupled receptor 183	Homo sapiens	EC50	=	104.88	nM	EUbOPEN Chemogenomics Library - GPCR Dose-Respose
NPT30125	Single protein	C5a anaphylatoxin chemotactic receptor	Homo sapiens	%Max (Mean)	=	-2.435	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT599	Individual protein	Nuclear receptor ROR-alpha	Homo sapiens	Ki	=	12.0	nM	DOI[10.1039/C3MD00005B]
NPT4358	Individual protein	Type-1 angiotensin II receptor	Homo sapiens	%Inhib (Mean)	=	-41.42	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT23094	Single protein	C-X3-C chemokine receptor 1	Homo sapiens	%Inhib (Mean)	=	-43.01	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT23094	Single protein	C-X3-C chemokine receptor 1	Homo sapiens	%Max (Mean)	=	-2.9	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT4358	Individual protein	Type-1 angiotensin II receptor	Homo sapiens	%Max (Mean)	=	2.21	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT4003	Individual protein	G-protein coupled receptor 120	Homo sapiens	%Max (Mean)	=	-1.859	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT4003	Individual protein	G-protein coupled receptor 120	Homo sapiens	%Inhib (Mean)	=	-35.14	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT6035	Individual protein	Sphingosine 1-phosphate receptor Edg-1	Homo sapiens	%Inhib (Mean)	=	-36.5	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT6197	Individual protein	Glucose-dependent insulinotropic receptor	Homo sapiens	%Max (Mean)	=	-3.686	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT6197	Individual protein	Glucose-dependent insulinotropic receptor	Homo sapiens	%Inhib (Mean)	=	-24.81	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT29660	Single protein	Adhesion G-protein coupled receptor F1	Homo sapiens	%Max (Mean)	=	43.52	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT29660	Single protein	Adhesion G-protein coupled receptor F1	Homo sapiens	%Inhib (Mean)	=	-11.29	%	GPCR results for EUbOPEN Chemogenomics Library 3
NPT6035	Individual protein	Sphingosine 1-phosphate receptor Edg-1	Homo sapiens	%Max (Mean)	=	2.27	%	GPCR results for EUbOPEN Chemogenomics Library 3

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	15500.0	nM	PMID[21797280]
NPT76	Cell line	C6	Rattus norvegicus	IC50	=	40000.0	nM	PMID[24211631]
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.95	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.98	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.85	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.96	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	-0.21	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT2615	Cell line	HEK-293T	Homo sapiens	Growth Rate	=	0.84	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT1045	Cell line	U2OS	Homo sapiens	Growth Rate	=	0.03	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>=	160000.0	nM	PMID[24211631]
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.24	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.56	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.5	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.43	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.84	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.91	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	0.52	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)
NPT29444	Cell line	Fibroblast	Homo sapiens	Growth Rate	=	-0.09	n.a.	Tm Shift (DSF) assay results for EUbOPEN Chemogenomis Library 2 (Incucyte)

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC109546 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	25411
0.1-0.2	22144
0.2-0.3	2051
0.3-0.4	150
0.4-0.5	57
0.5-0.6	27
0.6-0.7	5
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC47982
0.84	Intermediate Similarity	NPC317927
0.8333	Intermediate Similarity	NPC81306
0.7843	Intermediate Similarity	NPC84694
0.7843	Intermediate Similarity	NPC28862
0.7843	Intermediate Similarity	NPC143182
0.7692	Intermediate Similarity	NPC23852
0.7647	Intermediate Similarity	NPC189972
0.7407	Intermediate Similarity	NPC474634
0.717	Intermediate Similarity	NPC609126
0.7143	Intermediate Similarity	NPC475789
0.6727	Remote Similarity	NPC234193
0.6667	Remote Similarity	NPC136188
0.6667	Remote Similarity	NPC28657
0.6316	Remote Similarity	NPC31564
0.6034	Remote Similarity	NPC209620
0.5833	Remote Similarity	NPC152808
0.5789	Remote Similarity	NPC183927
0.5763	Remote Similarity	NPC321381
0.5667	Remote Similarity	NPC6391
0.5614	Remote Similarity	NPC244488
0.5593	Remote Similarity	NPC155986
0.5538	Remote Similarity	NPC218186
0.5484	Remote Similarity	NPC293287
0.5439	Remote Similarity	NPC162742
0.5439	Remote Similarity	NPC304309
0.5439	Remote Similarity	NPC470228
0.541	Remote Similarity	NPC50964
0.5345	Remote Similarity	NPC22105
0.5345	Remote Similarity	NPC34019
0.5345	Remote Similarity	NPC107059
0.5254	Remote Similarity	NPC474216
0.5172	Remote Similarity	NPC158208
0.5167	Remote Similarity	NPC230301
0.5167	Remote Similarity	NPC198968
0.5167	Remote Similarity	NPC285893
0.5167	Remote Similarity	NPC134847
0.5082	Remote Similarity	NPC241290
0.5082	Remote Similarity	NPC164840
0.5082	Remote Similarity	NPC484739
0.5082	Remote Similarity	NPC209944
0.5079	Remote Similarity	NPC474752
0.5079	Remote Similarity	NPC474683

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC109546 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7784
0.1-0.2	1253
0.2-0.3	79
0.3-0.4	24
0.4-0.5	7
0.5-0.6	2
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6667	Remote Similarity	NPD6942	Phase 4
0.5517	Remote Similarity	NPD4751	Phase 2
0.5167	Remote Similarity	NPD7339	Approved

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