NPASS Compound

Natural Product: NPC473644

Natural Product ID	NPC473644
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Acacetin7-O-Alpha-L-Rhamnopyranosyl-(1->6)-Beta-D-Glucopyranoside
IUPAC Name	7-[(2S,3R,4S,5S,6R)-6-[[(2R,3R,4R,5R,6S)-3,4-dihydroxy-5,6-dimethyloxan-2-yl]oxymethyl]-4,5-dihydroxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448038
PubChem CID	44575351
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 12.6366 0.9664 2.1376 C 0 0 0 0 0 0 0 0 0 0 0 0 11.4172 0.3970 2.5375 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2082 0.5448 1.9129 C 0 0 0 0 0 0 0 0 0 0 0 0 10.0994 1.3060 0.7833 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8680 1.4562 0.1478 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7214 0.8706 0.5973 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8394 0.0900 1.7582 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0493 -0.0613 2.3883 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4137 1.0005 -0.0335 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3656 0.4174 0.4919 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1739 0.5145 -0.0503 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0856 -0.1203 0.5414 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8033 -0.0409 -0.0035 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7496 -0.6844 0.6177 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5723 -0.7612 0.2161 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3291 0.1784 0.9581 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5772 0.2899 0.3313 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2745 1.5002 0.9081 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5014 1.6488 0.2749 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1874 2.7580 0.7509 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4574 2.4683 1.2085 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0523 3.5244 1.8805 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6284 3.4490 3.3332 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6484 4.8083 1.2273 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5379 4.5234 -0.2764 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2372 3.7485 -0.4240 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1386 4.5979 -0.2668 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4468 5.6900 -1.0131 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5897 5.9433 1.4552 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4112 -0.9546 0.6481 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4934 -1.9466 1.3279 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2480 -2.0914 0.4627 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6847 -2.5859 -0.7520 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0944 -3.8054 -1.0745 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4582 -3.7065 -2.2848 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1205 -4.8902 -2.7152 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4210 -5.2194 -2.0200 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8438 -6.0415 -2.7300 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2222 -5.5378 -2.3843 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1714 -4.8563 -1.0349 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0304 -5.7325 0.0217 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1466 -6.5829 -2.3956 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9482 -6.6507 -3.9838 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1605 -1.5356 2.6152 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9306 -1.4976 -0.5096 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5985 0.6793 -1.1529 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6802 1.3162 -1.7497 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9313 1.2280 -1.2020 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0143 1.8742 -1.8110 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7908 2.5173 -2.8512 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2360 1.7374 -1.1985 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4832 2.0574 -2.9268 O 0 0 0 0 0 0 0 0 0 0 0 0 13.4580 0.3362 2.5906 H 0 0 0 0 0 0 0 0 0 0 0 0 12.7283 1.0080 1.0438 H 0 0 0 0 0 0 0 0 0 0 0 0 12.8031 1.9762 2.5718 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9855 1.8077 0.3660 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8651 2.0675 -0.7285 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9384 -0.3790 2.1238 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1515 -0.6695 3.3005 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2615 -0.6790 1.4386 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6908 -0.4162 -0.8480 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4692 0.3650 -0.7650 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7109 2.4372 0.6945 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3402 1.4389 2.0106 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5545 3.2049 1.5648 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1728 3.4192 1.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7265 2.8105 3.4804 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3989 4.4241 3.7766 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4621 2.9176 3.8722 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6006 5.0456 1.5735 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3715 3.8652 -0.5506 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1520 3.1867 -1.3400 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5952 4.5770 -1.0924 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9128 5.4681 -1.8353 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4189 5.7266 2.1444 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0477 6.2561 0.4745 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9956 6.8359 1.7730 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2706 -0.6743 1.2905 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9793 -2.9470 1.3244 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5040 -2.7476 0.9559 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4025 -4.0474 -0.2201 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4064 -4.7166 -3.7936 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3870 -5.0885 -0.9260 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2603 -4.6425 -2.4854 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6436 -6.2849 -2.3180 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5727 -6.8597 -2.0096 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5209 -4.7582 -3.1270 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1987 -4.3994 -0.9122 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9391 -6.6684 -0.2366 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7075 -7.4153 -2.7117 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0286 -6.7792 -4.3193 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9495 -1.2283 3.1111 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8059 -1.0989 -0.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6297 0.7873 -1.6306 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0840 2.2281 -1.6578 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2124 1.5122 -3.7441 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 2 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 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 24 29 1 0 17 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 36 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 39 42 1 0 38 43 1 0 31 44 1 0 30 45 1 0 13 46 2 0 46 47 1 0 47 48 2 0 48 49 1 0 49 50 2 0 49 51 1 0 47 52 1 0 8 3 1 0 51 9 2 0 48 11 1 0 32 15 1 0 40 34 1 0 26 20 1 0 1 53 1 0 1 54 1 0 1 55 1 0 4 56 1 0 5 57 1 0 7 58 1 0 8 59 1 0 12 60 1 0 15 61 1 6 17 62 1 6 18 63 1 0 18 64 1 0 20 65 1 1 22 66 1 1 23 67 1 0 23 68 1 0 23 69 1 0 24 70 1 1 25 71 1 6 26 72 1 6 27 73 1 0 28 74 1 0 29 75 1 0 29 76 1 0 29 77 1 0 30 78 1 1 31 79 1 1 32 80 1 1 34 81 1 1 36 82 1 6 37 83 1 0 37 84 1 0 37 85 1 0 38 86 1 1 39 87 1 6 40 88 1 1 41 89 1 0 42 90 1 0 43 91 1 0 44 92 1 0 45 93 1 0 46 94 1 0 51 95 1 0 52 96 1 0 M END

Standard InCHIKey	DAVSWEXXVXXTSA-VLTOYACXSA-N
Standard InCHI	InChI=1S/C35H44O17/c1-13-14(2)47-33(30(43)25(13)38)46-12-23-27(40)29(42)32(52-34-31(44)28(41)26(39)15(3)48-34)35(51-23)49-18-9-19(36)24-20(37)11-21(50-22(24)10-18)16-5-7-17(45-4)8-6-16/h5-11,13-15,23,25-36,38-44H,12H2,1-4H3/t13-,14-,15-,23+,25+,26-,27+,28+,29-,30+,31+,32+,33+,34-,35+/m0/s1
SMILES	COc1ccc(cc1)c1oc2cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@@H]([C@H]([C@H]4O)O)C)[C@H]([C@@H]([C@H]3O[C@@H]3O[C@@H](C)[C@@H]([C@H]([C@H]3O)O)O)O)O)cc(c2c(=O)c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	736.26	Volume:	690.919 ? Van der Waals volume.
Dense:	1.066	LogP:	1.196 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.731 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.634 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	36.0
TPSA:	256.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	17.0
H-Bond Donor:	8.0	Rings:	6.0
Heavy Atoms:	17.0

MedChem Properties

QED Drug-Likeness Score:	0.136	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.246	Fsp³:	0.571
MCE-18:	145.364 ? 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:	0.659	Fluc inhibitor:	0.522 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.873 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.339 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.136	Promiscuous compounds:	0.306

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.297	MDCK Permeability:	-5.212
Pgp-inhibitor:	0.0	Pgp-substrate:	0.916
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):	0.981
20% Bioavailability (F20%):	0.361	30% Bioavailability (F30%):	0.989
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.273
Plasma Protein Binding (PPB):	85.178%	Volume Distribution (VD):	-0.162
Fu:	12.948% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.1
BSEP inhibitor:	0.005

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.981
HLM stability:	0.018 ? 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):

1.177

Half-life (T1/2):

4.221

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.156
Human Hepatotoxicity (H-HT):	0.26	Drug-induced Liver Injury (DILI):	0.972
AMES Toxicity:	0.882	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.005	Skin Sensitization:	0.954
Carcinogencity:	0.033	Eye Corrosion:	0.0
Eye Irritation:	0.058	Respiratory Toxicity:	0.002
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.979
Hematotoxicity:	0.124	Drug-induced Nephrotoxicity:	0.6
Genotoxicity:	0.217	RPMI-8226 Immunitoxicity:	0.284
A549 Cytotoxicity:	0.238	Hek293 Cytotoxicity:	0.301
BCF:	0.421 ? 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:	3.177 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.738 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.878 ? 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
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	flowers	bought from a drugstore in Beijing	n.a.	PMID[10514305]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	flower buds	n.a.	n.a.	PMID[14738377]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	flowers	n.a.	n.a.	PMID[21524582]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11577	Buddleja officinalis	Species	Scrophulariaceae	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
Inhibition	2

Activity Type	# Activity
Individual protein	1
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT183	Individual protein	Arachidonate 5-lipoxygenase	Rattus norvegicus	Inhibition	=	0.0	%	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Inhibition	=	16.8	%	PMID[15711537]

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 NPC473644 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	15274
0.1-0.2	30553
0.2-0.3	3309
0.3-0.4	462
0.4-0.5	191
0.5-0.6	39
0.6-0.7	12
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8421	Intermediate Similarity	NPC11468
0.8081	Intermediate Similarity	NPC311850
0.7979	Intermediate Similarity	NPC473623
0.7843	Intermediate Similarity	NPC68592
0.7553	Intermediate Similarity	NPC22062
0.7553	Intermediate Similarity	NPC473634
0.7553	Intermediate Similarity	NPC138811
0.7333	Intermediate Similarity	NPC488086
0.7308	Intermediate Similarity	NPC488087
0.7308	Intermediate Similarity	NPC488083
0.7264	Intermediate Similarity	NPC198199
0.7248	Intermediate Similarity	NPC262222
0.7103	Intermediate Similarity	NPC298666
0.7064	Intermediate Similarity	NPC120952
0.6733	Remote Similarity	NPC209296
0.6606	Remote Similarity	NPC488088
0.6566	Remote Similarity	NPC44931
0.6505	Remote Similarity	NPC142142
0.65	Remote Similarity	NPC65003
0.6442	Remote Similarity	NPC475382
0.6346	Remote Similarity	NPC488089
0.6337	Remote Similarity	NPC210073
0.6286	Remote Similarity	NPC195257
0.6275	Remote Similarity	NPC204693
0.6275	Remote Similarity	NPC115674
0.619	Remote Similarity	NPC479766
0.596	Remote Similarity	NPC80188
0.5893	Remote Similarity	NPC480441
0.5893	Remote Similarity	NPC25523
0.5816	Remote Similarity	NPC181712
0.5755	Remote Similarity	NPC46202
0.5728	Remote Similarity	NPC8856
0.5714	Remote Similarity	NPC95090
0.5714	Remote Similarity	NPC27408
0.5636	Remote Similarity	NPC101636
0.551	Remote Similarity	NPC331652
0.5472	Remote Similarity	NPC67105
0.5446	Remote Similarity	NPC135358
0.5413	Remote Similarity	NPC12013
0.5413	Remote Similarity	NPC11432
0.5413	Remote Similarity	NPC477613
0.5372	Remote Similarity	NPC209550
0.5364	Remote Similarity	NPC122467
0.5364	Remote Similarity	NPC483707
0.5351	Remote Similarity	NPC89052
0.5327	Remote Similarity	NPC227508
0.5321	Remote Similarity	NPC240306
0.53	Remote Similarity	NPC19709
0.5229	Remote Similarity	NPC122809
0.5229	Remote Similarity	NPC186816
0.5221	Remote Similarity	NPC298171
0.52	Remote Similarity	NPC473043
0.5189	Remote Similarity	NPC211594
0.5182	Remote Similarity	NPC475366
0.5175	Remote Similarity	NPC602448
0.5146	Remote Similarity	NPC27942
0.5143	Remote Similarity	NPC220169
0.5135	Remote Similarity	NPC65711
0.5091	Remote Similarity	NPC257566
0.5088	Remote Similarity	NPC221342
0.5088	Remote Similarity	NPC476470
0.5056	Remote Similarity	NPC29353
0.5048	Remote Similarity	NPC22832
0.5048	Remote Similarity	NPC243930
0.5045	Remote Similarity	NPC64051

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473644 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4692
0.1-0.2	4397
0.2-0.3	52
0.3-0.4	4
0.4-0.5	3
0.5-0.6	1
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
0.6733	Remote Similarity	NPD7054	Phase 4
0.5086	Remote Similarity	NPD7472	Pre-clinical

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