NPASS Compound

Natural Product: NPC173347

Natural Product ID	NPC173347
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(14R,17S,20S,22R)-14,17,20-Trihydroxy-3Beta-(O-Beta-D-Glucopyranosyl)-1-Oxowitha-5,24-Dienolide
IUPAC Name	(2R)-2-[(1S)-1-[(3R,8R,9S,10R,13S,14R,17S)-14,17-dihydroxy-10,13-dimethyl-1-oxo-3-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,3,4,7,8,9,11,12,15,16-decahydrocyclopenta[a]phenanthren-17-yl]-1-hydroxyethyl]-4,5-dimethyl-2,3-dihydropyran-6-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL501881
PubChem CID	10508451
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives [CHEMONTID:0001561] Withanolide glycosides 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 96101 0 0 0 0 0 0 0 0999 V2000 -9.6148 -0.3420 2.3051 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4715 0.1710 1.4712 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7736 0.7574 0.3379 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2212 0.8913 -0.0715 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7150 1.2724 -0.5307 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9837 1.8334 -1.6101 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4048 1.0842 -0.0534 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1872 -0.1071 0.7301 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.0749 0.0284 1.9182 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6907 -0.0552 1.1129 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4595 -1.2064 2.0165 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9281 -0.0090 -0.1602 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1548 -1.2416 -1.0070 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8989 -1.2119 -1.9032 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8776 -0.9108 -0.8735 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5127 -0.5161 -1.3606 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0600 -1.8010 -1.9950 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5100 -1.6548 -2.1519 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2590 -0.7376 -1.5060 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7265 -0.6714 -1.7358 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4428 -0.8970 -0.4527 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5533 -0.7987 0.7724 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5788 0.3078 0.6418 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4591 1.2429 1.4008 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6675 0.2414 -0.5482 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6382 1.5879 -1.2205 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3074 -0.2719 -0.1476 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2838 0.5839 0.9059 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7725 0.4380 1.1352 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4809 0.2561 -0.1341 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1448 1.4998 -0.9822 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4929 -0.0140 -0.2379 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7260 -0.5909 -0.0834 C 0 0 1 0 0 0 0 0 0 0 0 0 7.6336 0.0382 -1.1450 C 0 0 1 0 0 0 0 0 0 0 0 0 8.2180 1.3397 -0.5746 C 0 0 2 0 0 0 0 0 0 0 0 0 9.1568 1.0063 0.5666 C 0 0 1 0 0 0 0 0 0 0 0 0 8.5584 -0.1798 1.2951 C 0 0 1 0 0 0 0 0 0 0 0 0 8.8693 0.0218 2.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2675 0.0818 2.9007 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1952 -0.2369 1.1788 O 0 0 0 0 0 0 0 0 0 0 0 0 10.3916 0.6927 0.0031 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1526 2.1326 -0.1799 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6377 -0.8298 -1.5333 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6797 -2.0433 -0.1023 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5031 1.0486 -0.9229 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5912 1.1229 1.8466 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9657 -1.3159 1.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4001 0.4067 2.4362 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2048 -0.5733 3.3077 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3064 1.2713 -1.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6151 -0.1617 -0.0750 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7906 1.4411 0.6844 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3549 -1.0188 0.1610 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0751 -0.8271 2.6215 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8122 0.9835 2.4282 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3960 -1.7960 2.2664 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1232 -0.8236 3.0029 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6592 -1.9138 1.7148 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1039 -2.1831 -0.4639 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0776 -1.1455 -1.6345 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0075 -0.4948 -2.7166 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7945 -2.2553 -2.3011 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5125 0.2285 -2.1426 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4826 -1.9784 -2.9410 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2142 -2.6293 -1.3057 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0212 -2.3270 -2.8333 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9336 0.3228 -2.1926 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9838 -1.4929 -2.4538 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8762 -1.9160 -0.4516 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9730 -1.7314 0.9415 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1559 -0.6205 1.6832 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8530 1.6853 -1.9911 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6193 1.7640 -1.7091 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4232 2.3588 -0.4456 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5164 -1.2862 0.3266 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1947 0.2800 1.8893 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0270 1.6643 0.8332 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9675 -0.2768 1.9428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0881 1.4465 1.5480 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9311 2.2531 -0.6675 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3557 1.3219 -2.0635 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1820 1.9317 -0.7540 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7312 -1.6851 -0.1505 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0476 0.3486 -2.0320 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7242 1.8352 -1.4160 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1814 1.8586 1.2549 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0537 -1.1284 1.0089 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4090 -0.7239 3.4259 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4902 1.0377 3.0533 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5661 0.9317 2.4736 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5356 1.1452 -0.8669 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2292 2.4921 0.7204 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5739 -0.9673 -2.5102 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3914 -1.8750 0.8170 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4629 0.8700 -1.8807 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9217 1.9148 1.3786 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 8 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 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 6 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 6 21 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 37 40 1 0 36 41 1 0 35 42 1 0 34 43 1 0 15 44 1 1 12 45 1 6 10 46 1 1 9 2 1 0 30 12 1 0 40 33 1 0 30 15 1 0 27 16 1 0 25 19 1 0 1 47 1 0 1 48 1 0 1 49 1 0 4 50 1 0 4 51 1 0 4 52 1 0 8 53 1 6 9 54 1 0 9 55 1 0 11 56 1 0 11 57 1 0 11 58 1 0 13 59 1 0 13 60 1 0 14 61 1 0 14 62 1 0 16 63 1 6 17 64 1 0 17 65 1 0 18 66 1 0 20 67 1 0 20 68 1 0 21 69 1 6 22 70 1 0 22 71 1 0 26 72 1 0 26 73 1 0 26 74 1 0 27 75 1 1 28 76 1 0 28 77 1 0 29 78 1 0 29 79 1 0 31 80 1 0 31 81 1 0 31 82 1 0 33 83 1 1 34 84 1 6 35 85 1 6 36 86 1 1 37 87 1 6 38 88 1 0 38 89 1 0 39 90 1 0 41 91 1 0 42 92 1 0 43 93 1 0 44 94 1 0 45 95 1 0 46 96 1 0 M END

Standard InCHIKey	SYYXVJIFABSJBU-MJJWKRKWSA-N
Standard InCHI	InChI=1S/C34H50O12/c1-16-12-24(46-28(40)17(16)2)32(5,41)34(43)11-10-33(42)21-7-6-18-13-19(44-29-27(39)26(38)25(37)22(15-35)45-29)14-23(36)31(18,4)20(21)8-9-30(33,34)3/h6,19-22,24-27,29,35,37-39,41-43H,7-15H2,1-5H3/t19-,20+,21-,22-,24-,25-,26+,27-,29-,30+,31+,32+,33-,34+/m1/s1
SMILES	CC1=C(C)C(=O)O[C@H](C1)[C@@](C)([C@@]1(CC[C@]2([C@@H]3CC=C4C[C@H](CC(=O)[C@]4(C)[C@H]3CC[C@]12C)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	650.33	Volume:	640.218 ? Van der Waals volume.
Dense:	1.016	LogP:	0.18 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.942 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.37 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	34.0
TPSA:	203.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.161	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.762	Fsp³:	0.824
MCE-18:	125.839 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.871	Fluc inhibitor:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.178	Promiscuous compounds:	0.376

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.345	MDCK Permeability:	-5.265
Pgp-inhibitor:	0.0	Pgp-substrate:	0.962
PAMPA:	1.0 ? 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):	0.022
20% Bioavailability (F20%):	0.253	30% Bioavailability (F30%):	0.96
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.779
Plasma Protein Binding (PPB):	73.007%	Volume Distribution (VD):	-0.311
Fu:	23.932% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.243
BSEP inhibitor:	0.128

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.776	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.057
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.993
HLM stability:	0.263 ? 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):

1.98

Half-life (T1/2):

3.523

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.031
Human Hepatotoxicity (H-HT):	0.799	Drug-induced Liver Injury (DILI):	0.677
AMES Toxicity:	0.838	Rat Oral Acute Toxicity:	0.04
Maximum Recommended Daily Dose:	0.143	Skin Sensitization:	1.0
Carcinogencity:	0.742	Eye Corrosion:	0.0
Eye Irritation:	0.018	Respiratory Toxicity:	0.043
Drug-induced Neurotoxicity:	0.015	Ototoxicity:	0.954
Hematotoxicity:	0.427	Drug-induced Nephrotoxicity:	0.943
Genotoxicity:	0.911	RPMI-8226 Immunitoxicity:	0.134
A549 Cytotoxicity:	0.55	Hek293 Cytotoxicity:	0.499
BCF:	0.407 ? 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:	3.038 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.476 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.566 ? 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
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	fruits	n.a.	n.a.	PMID[18952419]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23316950]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13927	Withania coagulans	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13927	Withania coagulans	Species	Solanaceae	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
Activity	10
ED50	1

Activity Type	# Activity
Organism	11

Molecular-level activity

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

In vitro activity

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

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	22.7	%	PMID[17190442]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	44.1	%	PMID[24904961]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	14.7	%	PMID[24721727]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	25.7	%	DOI[10.1039/C1MD00105A]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	24.7	%	PMID[24904961]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	21.2	%	PMID[24904961]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	15.6	%	PMID[24904961]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	25.0	mg.kg-1	PMID[18955526]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	40.5	%	PMID[17638702]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	29.8	%	PMID[23398362]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	23.3	%	PMID[23398362]

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 NPC173347 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	18869
0.1-0.2	24921
0.2-0.3	5317
0.3-0.4	713
0.4-0.5	27
0.5-0.6	9
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	Natural Product ID
0.6098	Remote Similarity	NPC153440
0.5833	Remote Similarity	NPC270850
0.5833	Remote Similarity	NPC225826
0.5833	Remote Similarity	NPC305260
0.5581	Remote Similarity	NPC107493
0.5517	Remote Similarity	NPC103045
0.5312	Remote Similarity	NPC484715
0.5104	Remote Similarity	NPC318135
0.5056	Remote Similarity	NPC484743
0.5048	Remote Similarity	NPC484726

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC173347 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7087
0.1-0.2	1942
0.2-0.3	111
0.3-0.4	10
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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
		NPD

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