NPASS Compound

Natural Product: NPC547522

Natural Product ID	NPC547522
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S},3~{S},4~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0002934] Flavonoid O-glucuronides [CHEMONTID:0003534] Flavonoid-7-O-glucuronides

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 93 98 0 0 0 0 0 0 0 0999 V2000 -6.8941 -0.8536 3.1327 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0171 -0.0483 1.8503 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9786 0.8605 1.7300 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9571 1.3386 0.4246 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6706 0.2662 -0.4158 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3967 0.3836 -0.9871 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1007 -0.7420 -1.9337 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.8286 -0.6123 -2.4048 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7876 -1.1276 -1.7141 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1978 -0.1014 -0.9104 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1308 0.0589 -0.6562 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9816 0.7770 -1.4353 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5779 1.4739 -2.6306 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6777 1.7893 -2.9675 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0269 2.4161 -4.1664 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0229 2.7246 -5.0415 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3313 3.3502 -6.2483 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3033 2.4229 -4.7464 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2570 2.7726 -5.6860 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5813 1.8078 -3.5580 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2870 0.8515 -1.0824 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7916 0.2897 -0.0494 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1539 0.4044 0.2666 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7068 -0.1901 1.3693 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0336 -0.0946 1.7012 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0501 0.5700 1.0247 C 0 0 2 0 0 0 0 0 0 0 0 0 8.0399 -0.3275 0.7097 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2526 -0.1218 1.3185 C 0 0 2 0 0 0 0 0 0 0 0 0 10.1855 -1.2295 1.0013 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7958 -2.1683 0.2811 O 0 0 0 0 0 0 0 0 0 0 0 0 11.4779 -1.2297 1.4942 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0690 -0.0350 2.8223 C 0 0 1 0 0 0 0 0 0 0 0 0 10.3097 0.1430 3.4434 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1702 1.1324 3.1327 C 0 0 2 0 0 0 0 0 0 0 0 0 7.1360 0.6391 3.9491 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5191 1.7085 1.9163 C 0 0 1 0 0 0 0 0 0 0 0 0 8.2928 2.6433 1.2423 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8993 -0.9334 2.2088 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5527 -1.0593 1.9153 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7398 -1.8056 2.7565 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 -0.4534 0.7956 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6728 -0.5614 0.4834 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0584 -1.2193 1.2273 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0929 -2.3012 -0.8234 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0204 -3.2024 -0.8186 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2597 -3.0349 -1.4989 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.4956 -4.2737 -0.9792 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4352 -2.0829 -1.3662 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5239 -2.6851 -1.9650 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1785 2.0867 0.0462 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.1043 3.3933 0.5479 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4568 1.4295 0.5014 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0005 0.6185 -0.4852 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3103 0.7344 1.8231 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.3687 -0.1622 1.9668 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8146 -0.8498 3.4028 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1683 -1.9062 2.9358 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4870 -0.4034 3.9530 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0342 -0.7570 1.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0724 2.0520 0.3248 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6868 0.3810 -0.1042 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3262 1.3730 -1.4300 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7864 -0.5958 -2.8016 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9859 -1.5270 -2.4190 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5003 1.6152 -2.2991 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0545 2.6310 -4.3648 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2698 3.3202 -7.0358 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0846 2.5281 -6.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6045 1.5651 -3.3254 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7319 0.9857 -0.4107 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7091 1.0281 0.0545 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7696 0.8164 0.9941 H 0 0 0 0 0 0 0 0 0 0 0 0 12.1581 -1.8929 1.1306 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6652 -0.9910 3.2123 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6628 -0.7239 3.7967 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7465 1.8832 3.7143 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5339 0.3664 4.8112 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5819 2.2411 2.2252 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2235 2.4751 0.2759 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3358 -1.3923 3.0658 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1881 -2.6294 3.1947 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4247 -2.0068 0.1885 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1073 -3.8335 -0.0321 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0313 -3.0744 -2.5792 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4020 -4.2481 0.0133 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6329 -1.9843 -0.2885 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2527 -2.0566 -2.1927 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2177 2.1744 -1.0590 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5941 3.4399 1.4193 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1967 2.2673 0.6557 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7138 0.0426 -0.1124 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3171 1.4776 2.6567 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2334 -1.0326 1.5641 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 1 0 18 20 2 0 12 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 2 0 29 31 1 0 28 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 24 38 2 0 38 39 1 0 39 40 1 0 39 41 2 0 41 42 1 0 42 43 2 0 9 44 1 0 44 45 1 0 44 46 1 0 46 47 1 0 46 48 1 0 48 49 1 0 4 50 1 0 50 51 1 0 50 52 1 0 52 53 1 0 52 54 1 0 54 55 1 0 54 2 1 0 48 7 1 0 42 11 1 0 20 13 1 0 41 22 1 0 36 26 1 0 1 56 1 0 1 57 1 0 1 58 1 0 2 59 1 6 4 60 1 1 6 61 1 0 6 62 1 0 7 63 1 6 9 64 1 6 14 65 1 0 15 66 1 0 17 67 1 0 19 68 1 0 20 69 1 0 23 70 1 0 26 71 1 6 28 72 1 6 31 73 1 0 32 74 1 1 33 75 1 0 34 76 1 1 35 77 1 0 36 78 1 1 37 79 1 0 38 80 1 0 40 81 1 0 44 82 1 1 45 83 1 0 46 84 1 6 47 85 1 0 48 86 1 1 49 87 1 0 50 88 1 6 51 89 1 0 52 90 1 1 53 91 1 0 54 92 1 1 55 93 1 0 M END

Standard InCHIKey	NYEMNXLOIMNTDU-KFDHYNOESA-N
Standard InCHI	InChI=1S/C33H38O22/c1-8-17(37)20(40)24(44)31(50-8)49-7-15-18(38)21(41)25(45)33(53-15)54-28-19(39)16-13(36)5-10(51-32-26(46)22(42)23(43)29(55-32)30(47)48)6-14(16)52-27(28)9-2-3-11(34)12(35)4-9/h2-6,8,15,17-18,20-26,29,31-38,40-46H,7H2,1H3,(H,47,48)/t8-,15+,17-,18+,20-,21-,22-,23-,24+,25+,26+,29-,31+,32+,33-/m0/s1
SMILES	C[C@@H]1O[C@@H](OC[C@H]2O[C@@H](OC3=C(C4=CC=C(O)C(O)=C4)OC4=CC(O[C@@H]5O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]5O)=CC(O)=C4C3=O)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	786.19	Volume:	697.642 ? Van der Waals volume.
Dense:	1.127	LogP:	-0.353 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.85 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.713 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	37.0
TPSA:	365.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	22.0
H-Bond Donor:	13.0	Rings:	6.0
Heavy Atoms:	22.0

MedChem Properties

QED Drug-Likeness Score:	0.092	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.449	Fsp³:	0.515
MCE-18:	158.4 ? 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:	1
Colloidal aggregators:	0.467	Fluc inhibitor:	0.312 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.843 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.645 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.232	Promiscuous compounds:	0.549

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.735	MDCK Permeability:	-4.929
Pgp-inhibitor:	0.0	Pgp-substrate:	0.794
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):	0.936
20% Bioavailability (F20%):	0.222	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.06
Plasma Protein Binding (PPB):	63.67%	Volume Distribution (VD):	-0.282
Fu:	32.13% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.908
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.013
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:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.717
HLM stability:	0.002 ? 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):

0.296

Half-life (T1/2):

7.514

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.03
Human Hepatotoxicity (H-HT):	0.493	Drug-induced Liver Injury (DILI):	0.996
AMES Toxicity:	0.641	Rat Oral Acute Toxicity:	0.002
Maximum Recommended Daily Dose:	0.004	Skin Sensitization:	0.999
Carcinogencity:	0.002	Eye Corrosion:	0.0
Eye Irritation:	0.069	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.996
Hematotoxicity:	0.03	Drug-induced Nephrotoxicity:	0.821
Genotoxicity:	0.799	RPMI-8226 Immunitoxicity:	0.067
A549 Cytotoxicity:	0.239	Hek293 Cytotoxicity:	0.033
BCF:	0.32 ? 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:	2.869 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.572 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.653 ? 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
NPO11984	Tulipa gesneriana	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25126881]
NPO11984	Tulipa gesneriana	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11984	Tulipa gesneriana	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11984	Tulipa gesneriana	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11984	Tulipa gesneriana	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11984	Tulipa gesneriana	Species	Liliaceae	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

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 NPC547522 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	21658
0.1-0.2	25315
0.2-0.3	2158
0.3-0.4	336
0.4-0.5	241
0.5-0.6	98
0.6-0.7	38
0.7-0.8	1
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
0.7579	Intermediate Similarity	NPC186816
0.7071	Intermediate Similarity	NPC470443
0.7048	Intermediate Similarity	NPC480441
0.701	Intermediate Similarity	NPC67105
0.6939	Remote Similarity	NPC203259
0.6939	Remote Similarity	NPC33054
0.6939	Remote Similarity	NPC210073
0.6939	Remote Similarity	NPC176740
0.6939	Remote Similarity	NPC471725
0.6939	Remote Similarity	NPC134532
0.6939	Remote Similarity	NPC602582
0.6863	Remote Similarity	NPC473073
0.6774	Remote Similarity	NPC271692
0.6667	Remote Similarity	NPC14187
0.6634	Remote Similarity	NPC126784
0.6634	Remote Similarity	NPC241423
0.6495	Remote Similarity	NPC605784
0.6422	Remote Similarity	NPC25523
0.6337	Remote Similarity	NPC173582
0.6337	Remote Similarity	NPC44931
0.6337	Remote Similarity	NPC265885
0.6337	Remote Similarity	NPC181465
0.6337	Remote Similarity	NPC215710
0.6337	Remote Similarity	NPC473438
0.6337	Remote Similarity	NPC227508
0.6337	Remote Similarity	NPC253788
0.6296	Remote Similarity	NPC121703
0.6286	Remote Similarity	NPC142142
0.6211	Remote Similarity	NPC249281
0.619	Remote Similarity	NPC229409
0.6176	Remote Similarity	NPC39834
0.6146	Remote Similarity	NPC136042
0.6132	Remote Similarity	NPC486577
0.6122	Remote Similarity	NPC235260
0.6122	Remote Similarity	NPC155763
0.6122	Remote Similarity	NPC20505
0.6117	Remote Similarity	NPC65563
0.6117	Remote Similarity	NPC470949
0.6117	Remote Similarity	NPC156869
0.61	Remote Similarity	NPC276377
0.6082	Remote Similarity	NPC46420
0.6019	Remote Similarity	NPC67326
0.5983	Remote Similarity	NPC209550
0.5979	Remote Similarity	NPC158674
0.5962	Remote Similarity	NPC22062
0.5962	Remote Similarity	NPC473634
0.5962	Remote Similarity	NPC138811
0.5926	Remote Similarity	NPC476472
0.5926	Remote Similarity	NPC294815
0.5926	Remote Similarity	NPC16194
0.5905	Remote Similarity	NPC473571
0.5905	Remote Similarity	NPC110941
0.5888	Remote Similarity	NPC122467
0.5888	Remote Similarity	NPC209296
0.5888	Remote Similarity	NPC473327
0.5882	Remote Similarity	NPC116864
0.5882	Remote Similarity	NPC244776
0.5849	Remote Similarity	NPC488073
0.5842	Remote Similarity	NPC116458
0.5842	Remote Similarity	NPC246943
0.581	Remote Similarity	NPC150164
0.58	Remote Similarity	NPC611303
0.5789	Remote Similarity	NPC277532
0.578	Remote Similarity	NPC89127
0.5758	Remote Similarity	NPC84362
0.5752	Remote Similarity	NPC292019
0.5752	Remote Similarity	NPC202908
0.5741	Remote Similarity	NPC32641
0.5741	Remote Similarity	NPC256188
0.5714	Remote Similarity	NPC238376
0.5701	Remote Similarity	NPC488074
0.5701	Remote Similarity	NPC64051
0.5648	Remote Similarity	NPC65711
0.5644	Remote Similarity	NPC282169
0.563	Remote Similarity	NPC480444
0.56	Remote Similarity	NPC27640
0.5596	Remote Similarity	NPC72016
0.5596	Remote Similarity	NPC35119
0.5566	Remote Similarity	NPC275454
0.5556	Remote Similarity	NPC127546
0.5556	Remote Similarity	NPC57625
0.5556	Remote Similarity	NPC19709
0.5556	Remote Similarity	NPC173637
0.5556	Remote Similarity	NPC317489
0.5556	Remote Similarity	NPC223424
0.5556	Remote Similarity	NPC600591
0.5536	Remote Similarity	NPC470446
0.5524	Remote Similarity	NPC251417
0.5514	Remote Similarity	NPC303913
0.55	Remote Similarity	NPC297987
0.5472	Remote Similarity	NPC471079
0.5455	Remote Similarity	NPC138990
0.5446	Remote Similarity	NPC470445
0.5431	Remote Similarity	NPC303694
0.5413	Remote Similarity	NPC46202
0.5413	Remote Similarity	NPC240306
0.541	Remote Similarity	NPC175429
0.5398	Remote Similarity	NPC253685
0.5392	Remote Similarity	NPC59534
0.5392	Remote Similarity	NPC138927
0.5364	Remote Similarity	NPC12013
0.5364	Remote Similarity	NPC11432
0.5364	Remote Similarity	NPC477613
0.5357	Remote Similarity	NPC471669
0.5315	Remote Similarity	NPC606657
0.531	Remote Similarity	NPC101636
0.5294	Remote Similarity	NPC305811
0.5288	Remote Similarity	NPC608742
0.5283	Remote Similarity	NPC265115
0.5259	Remote Similarity	NPC189564
0.5248	Remote Similarity	NPC289667
0.5229	Remote Similarity	NPC605592
0.5207	Remote Similarity	NPC480445
0.5203	Remote Similarity	NPC241781
0.5179	Remote Similarity	NPC37668
0.5175	Remote Similarity	NPC221342
0.5175	Remote Similarity	NPC476470
0.5172	Remote Similarity	NPC203145
0.5164	Remote Similarity	NPC162394
0.514	Remote Similarity	NPC95866
0.5135	Remote Similarity	NPC64425
0.513	Remote Similarity	NPC223426
0.513	Remote Similarity	NPC602448
0.5098	Remote Similarity	NPC108831
0.5098	Remote Similarity	NPC182634
0.5089	Remote Similarity	NPC483414
0.5089	Remote Similarity	NPC483415
0.5086	Remote Similarity	NPC81042
0.5049	Remote Similarity	NPC277205
0.5049	Remote Similarity	NPC37919
0.5047	Remote Similarity	NPC190003
0.5046	Remote Similarity	NPC480466
0.5046	Remote Similarity	NPC187379
0.5045	Remote Similarity	NPC204693
0.5044	Remote Similarity	NPC483416
0.5044	Remote Similarity	NPC473623
0.5043	Remote Similarity	NPC89052
0.5043	Remote Similarity	NPC11468
0.5041	Remote Similarity	NPC156785
0.504	Remote Similarity	NPC192539

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC547522 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4652
0.1-0.2	4449
0.2-0.3	40
0.3-0.4	2
0.4-0.5	3
0.5-0.6	1
0.6-0.7	2
0.7-0.8	1
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
0.7732	Intermediate Similarity	NPD7251	Phase 2
0.6939	Remote Similarity	NPD6797	Phase 2
0.6449	Remote Similarity	NPD7808	Phase 3
0.5888	Remote Similarity	NPD7054	Phase 4

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