NPASS Compound

Natural Product: NPC477094

Natural Product ID	NPC477094
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(1aR,2S,3R,4aR,6S,7S,7aS,8E,10R,11S,11aS)-1,1,3,6,9-Pentamethyl-2-acetoxy-4a,7a-epoxy-7,11-bis[[(E)-2-methyl-2-butenoyl]oxy]-10-(benzoyloxy)-1a,2,3,4,4a,5,6,7,7a,10,11,11a-dodecahydro-1H-cyclopenta[a]cyclopropa[f]cycloundecene-4-one
IUPAC Name	[(1R,3R,4S,5R,7S,8S,9R,10E,12S,13S,14S)-4-acetyloxy-3,6,6,10,14-pentamethyl-8,13-bis[[(E)-2-methylbut-2-enoyl]oxy]-2-oxo-16-oxatetracyclo[10.3.1.01,12.05,7]hexadec-10-en-9-yl] benzoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44179495
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids

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 97101 0 0 0 0 0 0 0 0999 V2000 -7.5928 0.8551 3.7564 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2807 0.2782 3.4188 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6498 0.5407 2.2905 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2388 1.4446 1.2875 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3407 -0.1090 2.0894 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8572 -0.8800 2.9682 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5845 0.0752 0.9687 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2903 -0.5591 0.7540 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3959 -1.1886 -0.5569 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7121 -2.2211 -1.2151 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7961 -2.6736 -0.4008 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6932 -3.3573 0.9202 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1819 -2.9768 -1.0043 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2703 -2.4334 -1.2608 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5206 -2.9931 -0.1697 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9652 -2.7882 -0.4439 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5763 -3.8000 -0.8681 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7412 -1.5454 -0.2660 C 0 0 1 0 0 0 0 0 0 0 0 0 3.9374 -1.4270 -1.2035 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6429 -0.0518 -1.8175 C 0 0 1 0 0 0 0 0 0 0 0 0 3.2694 0.7126 -0.5650 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3424 -0.3243 0.1264 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9270 -1.1336 1.0601 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9571 0.1108 0.1243 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0983 0.1152 1.1065 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3004 0.6058 0.8529 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4174 1.5581 -0.1418 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7903 2.8637 0.0735 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0401 3.1960 1.2732 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9146 3.8684 -0.9648 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3029 5.1511 -0.6681 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4246 6.1280 -1.6568 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1482 5.7977 -2.9656 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7528 4.5031 -3.2900 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6447 3.5662 -2.2818 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5067 -0.3785 2.4430 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4151 0.8084 0.2220 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9034 2.0036 0.7335 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2675 3.0394 0.4627 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1060 1.9744 1.5395 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5770 3.1090 2.0304 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8093 3.1058 2.8602 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8474 0.7267 1.8468 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8737 0.5476 -2.4239 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3638 -4.5392 -0.0900 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0079 -3.4765 -2.2877 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6462 -3.2256 -3.4454 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0486 -2.0579 -3.6624 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9253 -4.2500 -4.4922 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8616 1.6515 3.0514 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3767 0.0664 3.6824 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6214 1.2361 4.7944 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8414 -0.3984 4.1713 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2254 0.9951 0.9820 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5770 1.5390 0.4282 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4850 2.4298 1.7389 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1694 -1.1409 1.6510 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0967 -0.5423 -1.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0301 -2.2799 -2.3409 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6758 -4.4493 0.7221 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8660 -3.1319 1.5625 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6391 -3.1750 1.4869 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9324 -2.9129 -0.2174 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1544 -3.9446 -1.5490 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3899 -2.1720 -1.7352 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1948 -1.5976 -1.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3420 -2.6685 0.8362 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8587 -1.3165 -0.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9609 -2.2211 -1.9477 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8122 -0.1203 -2.5432 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7633 1.6529 -0.7623 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6048 0.5076 -0.8755 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5580 1.1071 1.8596 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5351 5.4731 0.3453 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7294 7.1396 -1.4339 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2253 6.5128 -3.7732 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5446 4.2846 -4.3323 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3368 2.5672 -2.5542 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0968 0.4449 2.9523 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3720 -0.5394 3.1113 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1809 -1.2401 2.4520 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0487 4.0382 1.8160 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5892 2.5088 2.3256 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5896 2.5652 3.7992 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1401 4.1485 3.0305 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3582 0.3371 0.9424 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4894 0.8308 2.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0681 -0.0487 2.0987 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7197 -0.1748 -2.2881 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1822 1.4700 -1.8574 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7652 0.7345 -3.5087 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3240 -4.8816 -0.8880 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1233 -4.8101 0.8665 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3382 -5.0476 -0.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3522 -5.1840 -4.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9873 -4.5713 -4.4948 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6087 -3.9672 -5.4958 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 9 10 1 0 10 11 1 0 11 12 1 0 11 13 1 0 10 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 25 36 1 0 21 37 1 0 37 38 1 0 38 39 2 0 38 40 1 0 40 41 2 0 41 42 1 0 40 43 1 0 20 44 1 0 15 45 1 0 14 46 1 0 46 47 1 0 47 48 2 0 47 49 1 0 26 8 1 0 11 9 1 0 22 18 1 0 18 23 1 1 35 30 1 0 1 50 1 0 1 51 1 0 1 52 1 0 2 53 1 0 4 54 1 0 4 55 1 0 4 56 1 0 8 57 1 1 9 58 1 6 10 59 1 6 12 60 1 0 12 61 1 0 12 62 1 0 13 63 1 0 13 64 1 0 13 65 1 0 14 66 1 6 15 67 1 1 19 68 1 0 19 69 1 0 20 70 1 6 21 71 1 6 24 72 1 0 26 73 1 1 31 74 1 0 32 75 1 0 33 76 1 0 34 77 1 0 35 78 1 0 36 79 1 0 36 80 1 0 36 81 1 0 41 82 1 0 42 83 1 0 42 84 1 0 42 85 1 0 43 86 1 0 43 87 1 0 43 88 1 0 44 89 1 0 44 90 1 0 44 91 1 0 45 92 1 0 45 93 1 0 45 94 1 0 49 95 1 0 49 96 1 0 49 97 1 0 M END

Standard InCHIKey	GYIJTMQVZGAZIB-DHJRGDPVSA-N
Standard InCHI	InChI=1S/C39H48O10/c1-11-20(3)34(42)47-31-28-27(37(28,9)10)30(45-25(8)40)24(7)32(41)38-19-23(6)33(48-35(43)21(4)12-2)39(38,49-38)18-22(5)29(31)46-36(44)26-16-14-13-15-17-26/h11-18,23-24,27-31,33H,19H2,1-10H3/b20-11+,21-12+,22-18+/t23-,24+,27-,28+,29+,30+,31-,33-,38-,39-/m0/s1
SMILES	C/C=C(\C)/C(=O)O[C@H]1[C@H]2[C@H](C2(C)C)[C@@H]([C@H](C(=O)[C@@]34C[C@@H]([C@@H]([C@@]3(O4)/C=C(/[C@H]1OC(=O)C5=CC=CC=C5)\C)OC(=O)/C(=C/C)/C)C)C)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	676.32	Volume:	699.219 ? Van der Waals volume.
Dense:	0.967	LogP:	4.506 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.868 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.032 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	32.0
TPSA:	134.8 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.113	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.944	Fsp³:	0.564
MCE-18:	139.131 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.944	Fluc inhibitor:	0.039 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.066 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.248	Promiscuous compounds:	0.276

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.224	MDCK Permeability:	-4.884
Pgp-inhibitor:	1.0	Pgp-substrate:	0.143
PAMPA:	0.387 ? 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%):	0.403	30% Bioavailability (F30%):	0.501
50% Bioavailability (F50%):	0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	1.0
Plasma Protein Binding (PPB):	96.051%	Volume Distribution (VD):	0.023
Fu:	4.117% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.858	BCRP inhibitor:	0.004
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.994
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.728
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.674
CYP3A4-inhibitor:	0.579	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.965 ? 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):

7.636

Half-life (T1/2):

0.86

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.275
Human Hepatotoxicity (H-HT):	0.273	Drug-induced Liver Injury (DILI):	0.748
AMES Toxicity:	0.378	Rat Oral Acute Toxicity:	0.226
Maximum Recommended Daily Dose:	0.082	Skin Sensitization:	0.992
Carcinogencity:	0.576	Eye Corrosion:	0.0
Eye Irritation:	0.027	Respiratory Toxicity:	0.028
Drug-induced Neurotoxicity:	0.08	Ototoxicity:	0.392
Hematotoxicity:	0.47	Drug-induced Nephrotoxicity:	0.899
Genotoxicity:	0.93	RPMI-8226 Immunitoxicity:	0.076
A549 Cytotoxicity:	0.324	Hek293 Cytotoxicity:	0.505
BCF:	1.399 ? 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:	4.504 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.394 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.988 ? 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
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	aerial parts	Yuanjiang, Yunnan Province, China	2008-APR	PMID[19438253]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	Stems	n.a.	n.a.	PMID[30730729]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12595	Euphorbia royleana	Species	Euphorbiaceae	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
IC50	1
Inhibition	3

Activity Type	# Activity
Others	4

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
NPT2	Others	Unspecified	n.a.	IC50	>	5	ug/ml	PMID[19438253]
NPT2	Others	Unspecified	n.a.	Inhibition	=	4.7	%	PMID[19438253]
NPT2	Others	Unspecified	n.a.	Inhibition	=	1.1	%	PMID[19438253]
NPT2	Others	Unspecified	n.a.	Inhibition	=	12.2	%	PMID[19438253]

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 NPC477094 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	15097
0.1-0.2	32470
0.2-0.3	1866
0.3-0.4	380
0.4-0.5	11
0.5-0.6	15
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8732	High Similarity	NPC477096
0.8472	Intermediate Similarity	NPC477095
0.7973	Intermediate Similarity	NPC29922
0.7375	Intermediate Similarity	NPC477097
0.7222	Intermediate Similarity	NPC477093
0.7176	Intermediate Similarity	NPC482195
0.716	Intermediate Similarity	NPC272004
0.716	Intermediate Similarity	NPC477101
0.716	Intermediate Similarity	NPC477099
0.7037	Intermediate Similarity	NPC482175
0.6986	Remote Similarity	NPC475277
0.6986	Remote Similarity	NPC482193
0.6757	Remote Similarity	NPC475495
0.6667	Remote Similarity	NPC482192
0.6538	Remote Similarity	NPC473522
0.6386	Remote Similarity	NPC482181
0.6341	Remote Similarity	NPC477100
0.6341	Remote Similarity	NPC477098
0.6071	Remote Similarity	NPC482182
0.5897	Remote Similarity	NPC482184
0.5897	Remote Similarity	NPC482185
0.5875	Remote Similarity	NPC482176
0.5823	Remote Similarity	NPC189556
0.5823	Remote Similarity	NPC477092
0.5732	Remote Similarity	NPC482174
0.5696	Remote Similarity	NPC482178
0.5696	Remote Similarity	NPC482177
0.5682	Remote Similarity	NPC482402
0.5625	Remote Similarity	NPC81761
0.5618	Remote Similarity	NPC482400
0.561	Remote Similarity	NPC482180
0.5432	Remote Similarity	NPC482179
0.5341	Remote Similarity	NPC482188
0.5233	Remote Similarity	NPC475305

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477094 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4137
0.1-0.2	4932
0.2-0.3	81
0.3-0.4	0
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