NPASS Compound

Natural Product: NPC540728

Natural Product ID	NPC540728
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-[[(2~{R},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic 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 101106 0 0 0 0 0 0 0 0999 V2000 2.6610 5.3657 2.9655 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2922 5.9705 1.6930 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7252 5.2463 0.6700 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4841 3.9114 0.6663 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9000 3.2210 -0.3746 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8783 1.7789 -0.4187 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2014 1.0090 -0.9683 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2870 1.6208 -1.4646 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5019 1.9160 -0.7324 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4898 1.1258 -1.2634 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7751 1.4920 -1.1041 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5459 0.9213 0.0558 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7930 -0.4014 0.0740 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7450 -1.2846 0.0294 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7655 -2.0035 -1.2008 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0017 -2.6972 -1.2408 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2910 -3.1643 -2.6217 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9571 -3.8803 -0.3056 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.1885 -4.0651 0.2782 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8222 -3.6688 0.6473 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8642 -4.6288 1.6529 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7815 -2.2669 1.1770 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8394 -2.0334 2.0585 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0369 2.9744 -1.2109 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9152 3.3247 -2.5750 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0815 3.7927 -0.4230 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2624 3.6501 0.9352 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6783 3.3931 -0.8358 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5719 3.7967 -2.1777 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0241 -0.3359 -0.9024 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8631 -1.1136 -1.3578 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1672 -0.9348 -0.3646 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3720 -2.2919 -0.3287 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3973 -3.1281 -0.8270 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5321 -2.8472 0.1964 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5117 -2.0032 0.7003 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6718 -2.4665 1.2147 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2142 -3.7309 1.3563 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9876 -3.8576 2.4824 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2326 -3.3022 2.4532 C 0 0 2 0 0 0 0 0 0 0 0 0 7.3212 -1.8183 2.5679 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7122 -1.0729 1.6086 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1095 -3.8123 1.3178 C 0 0 2 0 0 0 0 0 0 0 0 0 8.4688 -2.7346 0.5169 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3018 -4.7773 0.4694 C 0 0 2 0 0 0 0 0 0 0 0 0 8.0433 -5.0529 -0.6713 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0380 -4.0739 0.0911 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3124 -4.8599 -0.7881 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2620 -0.6364 0.6468 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1379 -0.0941 0.1364 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9232 1.1885 0.0752 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5442 3.9858 -1.4841 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7716 5.3650 -1.5353 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4049 6.0730 -2.6364 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2059 5.8286 -3.8143 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3521 5.9687 -0.4735 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5993 7.3641 -0.4953 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0788 4.4620 3.0964 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7502 5.2449 2.9358 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3894 6.1216 3.7710 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7658 3.3105 1.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2535 1.6549 0.3197 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3177 1.0726 -2.0239 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5793 1.4268 0.1006 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0984 1.3015 1.0338 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7855 -0.7585 0.0320 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7702 -1.9397 -0.9542 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7729 -2.3930 -3.2630 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4048 -3.6161 -3.0921 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0481 -3.9988 -2.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6911 -4.8174 -0.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1519 -4.6911 1.0558 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8880 -3.8251 0.0192 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2411 -5.3931 1.4587 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8310 -2.1773 1.7724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5548 -2.1933 3.0162 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0613 3.1911 -0.9137 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8083 3.2058 -2.9735 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2694 4.8647 -0.7182 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7144 4.4412 1.3413 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9270 3.8855 -0.1757 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9635 4.6775 -2.3239 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4585 -3.4008 -0.3969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7219 -3.9040 0.2405 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4161 -4.4964 1.3543 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7539 -3.7013 3.3906 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0267 -1.5396 3.6015 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4293 -1.5673 2.5088 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3677 -0.5436 1.0567 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0183 -4.3028 1.6417 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3409 -2.8473 0.0623 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1266 -5.7192 1.0081 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8273 -5.9527 -1.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3081 -3.1228 -0.4514 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6634 -5.7800 -0.7799 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0478 0.0118 1.0537 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0916 3.4517 -2.3116 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0168 4.7681 -4.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1730 6.4640 -4.6659 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3084 6.0229 -3.7162 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7308 7.8566 0.3946 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 1 0 6 7 2 0 7 8 1 0 8 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 16 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 11 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 7 30 1 0 30 31 2 0 30 32 1 0 32 33 2 0 33 34 1 0 33 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 40 43 1 0 43 44 1 0 43 45 1 0 45 46 1 0 45 47 1 0 47 48 1 0 36 49 1 0 49 50 2 0 50 51 1 0 5 52 2 0 52 53 1 0 53 54 1 0 54 55 1 0 53 56 2 0 56 57 1 0 56 3 1 0 51 6 1 0 28 9 1 0 50 32 1 0 22 14 1 0 47 38 1 0 1 58 1 0 1 59 1 0 1 60 1 0 4 61 1 0 9 62 1 1 11 63 1 6 12 64 1 0 12 65 1 0 14 66 1 1 16 67 1 1 17 68 1 0 17 69 1 0 17 70 1 0 18 71 1 6 19 72 1 0 20 73 1 6 21 74 1 0 22 75 1 1 23 76 1 0 24 77 1 1 25 78 1 0 26 79 1 6 27 80 1 0 28 81 1 1 29 82 1 0 34 83 1 0 35 84 1 0 38 85 1 1 40 86 1 1 41 87 1 0 41 88 1 0 42 89 1 0 43 90 1 1 44 91 1 0 45 92 1 1 46 93 1 0 47 94 1 6 48 95 1 0 49 96 1 0 52 97 1 0 55 98 1 0 55 99 1 0 55100 1 0 57101 1 0 M END

Standard InCHIKey	AKOYMFNXEITYAK-CTYXHILBSA-N
Standard InCHI	InChI=1S/C35H44O22/c1-10-20(38)25(43)28(46)33(52-10)51-9-18-23(41)27(45)30(48)35(56-18)57-32-24(42)19-13(37)6-12(53-34-29(47)26(44)22(40)17(8-36)55-34)7-14(19)54-31(32)11-4-15(49-2)21(39)16(5-11)50-3/h4-7,10,17-18,20,22-23,25-30,33-41,43-48H,8-9H2,1-3H3/t10-,17+,18-,20-,22-,23-,25-,26-,27+,28-,29+,30-,33+,34+,35-/m0/s1
SMILES	COC1=CC(C2=C(O[C@@H]3O[C@@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@H](O)[C@@H]4O)[C@H](O)[C@@H](O)[C@@H]3O)C(=O)C3=C(O)C=C(O[C@@H]4O[C@H](CO)[C@H](O)[C@H](O)[C@H]4O)C=C3O2)=CC(OC)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	816.23	Volume:	734.871 ? Van der Waals volume.
Dense:	1.111	LogP:	-0.715 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.444 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.381 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	36.0
TPSA:	346.81 ? Topological Polar Surface Area.	H-Bond Acceptor:	22.0
H-Bond Donor:	12.0	Rings:	6.0
Heavy Atoms:	22.0

MedChem Properties

QED Drug-Likeness Score:	0.088	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.452	Fsp³:	0.571
MCE-18:	156.0 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.628	Fluc inhibitor:	0.145 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.722 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.563 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.071	Promiscuous compounds:	0.526

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.522	MDCK Permeability:	-5.291
Pgp-inhibitor:	0.0	Pgp-substrate:	0.969
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):	1.0
20% Bioavailability (F20%):	0.973	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.354
Plasma Protein Binding (PPB):	80.74%	Volume Distribution (VD):	-0.129
Fu:	18.081% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.18
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.398
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.918
HLM stability:	0.015 ? 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):

0.781

Half-life (T1/2):

3.611

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.014
Human Hepatotoxicity (H-HT):	0.83	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.998	Rat Oral Acute Toxicity:	0.005
Maximum Recommended Daily Dose:	0.002	Skin Sensitization:	1.0
Carcinogencity:	0.099	Eye Corrosion:	0.0
Eye Irritation:	0.013	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.991
Hematotoxicity:	0.901	Drug-induced Nephrotoxicity:	0.984
Genotoxicity:	0.882	RPMI-8226 Immunitoxicity:	0.617
A549 Cytotoxicity:	0.995	Hek293 Cytotoxicity:	0.789
BCF:	0.269 ? 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:	3.02 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.74 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.791 ? 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
NPO49435	Limnanthes douglasii	Species	Limnanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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

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

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 NPC540728 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	22403
0.1-0.2	23144
0.2-0.3	3253
0.3-0.4	580
0.4-0.5	282
0.5-0.6	130
0.6-0.7	58
0.7-0.8	2
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
0.75	Intermediate Similarity	NPC186816
0.7129	Intermediate Similarity	NPC480441
0.7129	Intermediate Similarity	NPC25523
0.6739	Remote Similarity	NPC116458
0.6739	Remote Similarity	NPC246943
0.6739	Remote Similarity	NPC605784
0.6702	Remote Similarity	NPC251417
0.6633	Remote Similarity	NPC470443
0.66	Remote Similarity	NPC476472
0.66	Remote Similarity	NPC294815
0.66	Remote Similarity	NPC16194
0.6566	Remote Similarity	NPC209296
0.6495	Remote Similarity	NPC22062
0.6495	Remote Similarity	NPC473634
0.6495	Remote Similarity	NPC138811
0.6444	Remote Similarity	NPC289667
0.6415	Remote Similarity	NPC277532
0.6413	Remote Similarity	NPC325555
0.6413	Remote Similarity	NPC226304
0.6408	Remote Similarity	NPC14187
0.64	Remote Similarity	NPC473327
0.6392	Remote Similarity	NPC275454
0.6392	Remote Similarity	NPC67105
0.6392	Remote Similarity	NPC227508
0.6374	Remote Similarity	NPC297987
0.6374	Remote Similarity	NPC158674
0.6374	Remote Similarity	NPC136042
0.6344	Remote Similarity	NPC611303
0.6337	Remote Similarity	NPC142142
0.6327	Remote Similarity	NPC210073
0.6304	Remote Similarity	NPC46420
0.6304	Remote Similarity	NPC84362
0.6304	Remote Similarity	NPC271692
0.6289	Remote Similarity	NPC609888
0.6224	Remote Similarity	NPC173582
0.6224	Remote Similarity	NPC44931
0.6224	Remote Similarity	NPC265885
0.6224	Remote Similarity	NPC181465
0.6224	Remote Similarity	NPC215710
0.6224	Remote Similarity	NPC39834
0.6224	Remote Similarity	NPC473438
0.6224	Remote Similarity	NPC253788
0.62	Remote Similarity	NPC488073
0.62	Remote Similarity	NPC126784
0.62	Remote Similarity	NPC241423
0.6162	Remote Similarity	NPC203259
0.6162	Remote Similarity	NPC33054
0.6162	Remote Similarity	NPC176740
0.6162	Remote Similarity	NPC471725
0.6162	Remote Similarity	NPC134532
0.6162	Remote Similarity	NPC156869
0.6162	Remote Similarity	NPC602582
0.6129	Remote Similarity	NPC603655
0.61	Remote Similarity	NPC473571
0.61	Remote Similarity	NPC110941
0.6087	Remote Similarity	NPC249281
0.6078	Remote Similarity	NPC32641
0.6078	Remote Similarity	NPC256188
0.6078	Remote Similarity	NPC35119
0.604	Remote Similarity	NPC240306
0.6	Remote Similarity	NPC135358
0.5979	Remote Similarity	NPC276377
0.5962	Remote Similarity	NPC473073
0.5888	Remote Similarity	NPC121703
0.5842	Remote Similarity	NPC65563
0.5842	Remote Similarity	NPC470949
0.5842	Remote Similarity	NPC150164
0.5833	Remote Similarity	NPC189564
0.5826	Remote Similarity	NPC192539
0.578	Remote Similarity	NPC292019
0.578	Remote Similarity	NPC202908
0.5769	Remote Similarity	NPC606657
0.5752	Remote Similarity	NPC198199
0.5741	Remote Similarity	NPC203145
0.5728	Remote Similarity	NPC64425
0.5676	Remote Similarity	NPC311850
0.5603	Remote Similarity	NPC120952
0.5566	Remote Similarity	NPC486577
0.5556	Remote Similarity	NPC311830
0.5556	Remote Similarity	NPC602448
0.5545	Remote Similarity	NPC480463
0.5534	Remote Similarity	NPC479405
0.5534	Remote Similarity	NPC303913
0.5526	Remote Similarity	NPC68592
0.55	Remote Similarity	NPC203050
0.55	Remote Similarity	NPC488072
0.55	Remote Similarity	NPC225434
0.55	Remote Similarity	NPC601586
0.549	Remote Similarity	NPC480466
0.5481	Remote Similarity	NPC204693
0.5481	Remote Similarity	NPC479404
0.5472	Remote Similarity	NPC473623
0.5472	Remote Similarity	NPC72016
0.547	Remote Similarity	NPC209550
0.5455	Remote Similarity	NPC22832
0.5455	Remote Similarity	NPC89052
0.5455	Remote Similarity	NPC486578
0.5429	Remote Similarity	NPC153755
0.5421	Remote Similarity	NPC488089
0.5408	Remote Similarity	NPC472459
0.5377	Remote Similarity	NPC479403
0.5361	Remote Similarity	NPC95090
0.5361	Remote Similarity	NPC277205
0.5361	Remote Similarity	NPC27408
0.5361	Remote Similarity	NPC37919
0.5357	Remote Similarity	NPC173837
0.5354	Remote Similarity	NPC285197
0.5354	Remote Similarity	NPC488071
0.534	Remote Similarity	NPC471079
0.5339	Remote Similarity	NPC138990
0.5315	Remote Similarity	NPC11468
0.5306	Remote Similarity	NPC24043
0.53	Remote Similarity	NPC101026
0.53	Remote Similarity	NPC243930
0.53	Remote Similarity	NPC120099
0.53	Remote Similarity	NPC488077
0.53	Remote Similarity	NPC601144
0.5294	Remote Similarity	NPC175429
0.5288	Remote Similarity	NPC67326
0.5283	Remote Similarity	NPC488074
0.5259	Remote Similarity	NPC295625
0.5258	Remote Similarity	NPC261866
0.5254	Remote Similarity	NPC470720
0.5254	Remote Similarity	NPC488079
0.525	Remote Similarity	NPC262222
0.5248	Remote Similarity	NPC223747
0.5248	Remote Similarity	NPC607707
0.5238	Remote Similarity	NPC102028
0.5234	Remote Similarity	NPC65711
0.5229	Remote Similarity	NPC195257
0.5229	Remote Similarity	NPC475382
0.5227	Remote Similarity	NPC189589
0.5214	Remote Similarity	NPC298666
0.5204	Remote Similarity	NPC64305
0.5204	Remote Similarity	NPC323593
0.5204	Remote Similarity	NPC203500
0.5204	Remote Similarity	NPC189142
0.5204	Remote Similarity	NPC77660
0.5192	Remote Similarity	NPC187379
0.5182	Remote Similarity	NPC101636
0.5169	Remote Similarity	NPC470719
0.5169	Remote Similarity	NPC208769
0.5169	Remote Similarity	NPC470717
0.5152	Remote Similarity	NPC27640
0.5152	Remote Similarity	NPC349108
0.5149	Remote Similarity	NPC21666
0.514	Remote Similarity	NPC46202
0.514	Remote Similarity	NPC475366
0.5138	Remote Similarity	NPC5319
0.5135	Remote Similarity	NPC470446
0.5126	Remote Similarity	NPC488078
0.5102	Remote Similarity	NPC19388
0.5102	Remote Similarity	NPC240431
0.5102	Remote Similarity	NPC39360
0.5102	Remote Similarity	NPC77672
0.5102	Remote Similarity	NPC55786
0.5102	Remote Similarity	NPC133671
0.5102	Remote Similarity	NPC135391
0.5102	Remote Similarity	NPC29763
0.5102	Remote Similarity	NPC78263
0.5102	Remote Similarity	NPC210003
0.5102	Remote Similarity	NPC250069
0.5102	Remote Similarity	NPC238376
0.51	Remote Similarity	NPC42773
0.51	Remote Similarity	NPC59534
0.51	Remote Similarity	NPC45522
0.51	Remote Similarity	NPC599850
0.5093	Remote Similarity	NPC12013
0.5093	Remote Similarity	NPC11432
0.5093	Remote Similarity	NPC477613
0.5091	Remote Similarity	NPC220173
0.5089	Remote Similarity	NPC244875
0.5086	Remote Similarity	NPC470716
0.5086	Remote Similarity	NPC488083
0.5051	Remote Similarity	NPC145038
0.5051	Remote Similarity	NPC56077
0.5051	Remote Similarity	NPC281131
0.5051	Remote Similarity	NPC253662
0.5051	Remote Similarity	NPC265530
0.5051	Remote Similarity	NPC179950
0.5051	Remote Similarity	NPC88789
0.5051	Remote Similarity	NPC491374
0.505	Remote Similarity	NPC60735
0.505	Remote Similarity	NPC219904
0.505	Remote Similarity	NPC26230
0.5046	Remote Similarity	NPC122467
0.5045	Remote Similarity	NPC470449
0.5045	Remote Similarity	NPC470445
0.5043	Remote Similarity	NPC473644
0.5043	Remote Similarity	NPC470715
0.5043	Remote Similarity	NPC164704

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC540728 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5751
0.1-0.2	3333
0.2-0.3	56
0.3-0.4	4
0.4-0.5	0
0.5-0.6	2
0.6-0.7	2
0.7-0.8	2
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
0.7113	Intermediate Similarity	NPD7251	Phase 2
0.7	Intermediate Similarity	NPD7808	Phase 3
0.6566	Remote Similarity	NPD7054	Phase 4
0.6162	Remote Similarity	NPD6797	Phase 2
0.5315	Remote Similarity	NPD7472	Pre-clinical
0.5138	Remote Similarity	NPD7804	Clinical (unspecified phase)

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