NPASS Compound

Natural Product: NPC533617

Natural Product ID	NPC533617
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3-hydroxy-4-methoxy-phenyl)-7-methoxy-5-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{R},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	2-(3-hydroxy-4-methoxy-phenyl)-7-methoxy-5-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{R},5~{R},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{R})-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 100105 0 0 0 0 0 0 0 0999 V2000 -6.9795 -5.1780 1.2888 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7087 -3.8950 1.8614 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5967 -3.1660 1.3918 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3776 -1.9269 1.9773 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3044 -1.1891 1.5450 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9944 0.0462 2.0538 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6928 0.6365 3.1072 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7221 1.4479 2.6366 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5044 2.7818 2.6095 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2353 3.5439 3.7033 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5979 3.3027 3.5285 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0669 3.2137 2.5908 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3778 2.8679 1.4553 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4338 2.6958 3.8597 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0750 2.9416 3.8184 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8180 1.2871 4.1397 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6294 0.5239 4.2175 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4776 -1.7196 0.5314 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3943 -1.0037 0.0863 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1520 0.1119 0.5779 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6057 -1.5830 -0.9191 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5223 -0.8080 -1.3161 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6115 -0.7284 -0.4788 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1544 0.5470 -0.4892 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5090 0.6381 -0.3604 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9030 2.1171 -0.3850 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2529 2.2899 -0.2344 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5574 3.6456 -0.3350 C 0 0 2 0 0 0 0 0 0 0 0 0 5.4144 3.7914 -1.3898 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7546 3.6785 -1.1482 C 0 0 2 0 0 0 0 0 0 0 0 0 7.2214 2.2999 -0.7454 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2684 4.7491 -0.2016 C 0 0 2 0 0 0 0 0 0 0 0 0 8.0910 4.1183 0.7255 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1094 5.3335 0.5942 C 0 0 2 0 0 0 0 0 0 0 0 0 6.5420 5.9249 1.7732 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2054 4.1578 0.9312 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2562 4.5761 1.8612 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1723 -0.0717 -1.5274 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8636 0.6998 -2.6704 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6878 -1.4740 -1.6177 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7357 -2.4078 -1.4944 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6147 -1.8089 -0.6295 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2072 -2.1251 0.6308 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8653 -2.7912 -1.4626 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1053 -3.4418 -2.5131 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3171 -4.7683 -2.7835 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6909 -5.4522 -3.8147 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1861 -4.7528 -4.5996 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8348 -5.4101 -5.6449 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6513 -6.7676 -5.9662 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4338 -3.4213 -4.3711 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3322 -2.7718 -5.2017 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2273 -2.7766 -3.3140 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9395 -3.4424 -0.9799 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6864 -2.9396 -0.0509 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7882 -3.6762 0.4058 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9862 -5.4757 1.6562 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0725 -5.0826 0.1800 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2224 -5.9287 1.5405 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0698 -1.6007 2.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2430 -0.1845 3.6490 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9623 3.1733 1.6513 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8693 3.3270 4.7081 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0933 4.6298 3.4496 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9445 2.6119 4.1199 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0608 4.3354 2.6556 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7481 3.4200 0.7041 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8341 3.3617 4.6813 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6707 2.8325 2.9356 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2871 1.1570 5.1506 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0343 0.7516 3.4394 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2076 -0.8839 0.5918 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9338 0.2246 0.5723 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3755 2.6305 0.4353 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5787 2.4886 -1.4017 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5997 4.1998 -0.5326 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2625 3.8813 -2.1422 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7027 2.3031 0.2714 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0458 1.9136 -1.4147 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4081 1.5605 -0.6680 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8305 5.5107 -0.7336 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0527 4.3318 0.6017 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6128 6.0840 -0.0191 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3226 5.4833 2.1557 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8524 3.3672 1.3423 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3912 4.0559 2.6800 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2935 -0.0279 -1.4411 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3211 0.2427 -3.4256 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2962 -1.6262 -2.6385 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4090 -2.1275 -0.8249 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1365 -2.7528 -0.9144 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6031 -3.0413 0.5383 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0135 -5.3662 -2.1769 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8704 -6.4977 -4.0076 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2159 -6.8525 -6.6560 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5366 -7.0967 -6.5662 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5816 -7.4393 -5.1042 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1150 -1.9776 -5.7730 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0150 -1.7338 -3.2213 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9698 -4.6529 -0.0481 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 5 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 1 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 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 25 38 1 0 38 39 1 0 38 40 1 0 40 41 1 0 40 42 1 0 42 43 1 0 21 44 2 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 48 49 1 0 49 50 1 0 48 51 1 0 51 52 1 0 51 53 2 0 44 54 1 0 54 55 1 0 55 56 2 0 56 3 1 0 16 7 1 0 55 18 1 0 42 23 1 0 53 45 1 0 36 28 1 0 1 57 1 0 1 58 1 0 1 59 1 0 4 60 1 0 7 61 1 1 9 62 1 6 10 63 1 0 10 64 1 0 11 65 1 0 12 66 1 1 13 67 1 0 14 68 1 1 15 69 1 0 16 70 1 1 17 71 1 0 23 72 1 1 25 73 1 1 26 74 1 0 26 75 1 0 28 76 1 6 30 77 1 6 31 78 1 0 31 79 1 0 31 80 1 0 32 81 1 6 33 82 1 0 34 83 1 6 35 84 1 0 36 85 1 1 37 86 1 0 38 87 1 1 39 88 1 0 40 89 1 6 41 90 1 0 42 91 1 6 43 92 1 0 46 93 1 0 47 94 1 0 50 95 1 0 50 96 1 0 50 97 1 0 52 98 1 0 53 99 1 0 56100 1 0 M END

Standard InCHIKey	UOOULRKANCNCRM-LTPRNHMOSA-N
Standard InCHI	InChI=1S/C35H44O21/c1-11-21(38)25(42)28(45)33(51-11)50-10-19-23(40)27(44)30(47)35(55-19)56-32-24(41)20-16(52-31(32)12-4-5-15(49-3)14(37)6-12)7-13(48-2)8-17(20)53-34-29(46)26(43)22(39)18(9-36)54-34/h4-8,11,18-19,21-23,25-30,33-40,42-47H,9-10H2,1-3H3/t11-,18+,19-,21+,22+,23+,25+,26+,27-,28-,29+,30-,33-,34-,35+/m1/s1
SMILES	COC1=CC(O[C@@H]2O[C@@H](CO)[C@H](O)[C@H](O)[C@@H]2O)=C2C(=O)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(C3=CC=C(OC)C(O)=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	800.24	Volume:	726.08 ? Van der Waals volume.
Dense:	1.102	LogP:	0.293 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.246 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.79 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	36.0
TPSA:	326.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	21.0
H-Bond Donor:	11.0	Rings:	6.0
Heavy Atoms:	21.0

MedChem Properties

QED Drug-Likeness Score:	0.089	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.378	Fsp³:	0.571
MCE-18:	152.455 ? 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:	0.623	Fluc inhibitor:	0.223 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.692 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.4 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.066	Promiscuous compounds:	0.342

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.649	MDCK Permeability:	-5.237
Pgp-inhibitor:	0.0	Pgp-substrate:	0.966
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%):	0.986	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.242
Plasma Protein Binding (PPB):	76.171%	Volume Distribution (VD):	-0.15
Fu:	20.879% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.619
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.054
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.85
HLM stability:	0.11 ? 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):

0.843

Half-life (T1/2):

3.57

ADMET: Toxicity

hERG Blockers:	0.003	hERG Blockers (10um):	0.029
Human Hepatotoxicity (H-HT):	0.733	Drug-induced Liver Injury (DILI):	0.987
AMES Toxicity:	0.997	Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.005	Skin Sensitization:	1.0
Carcinogencity:	0.082	Eye Corrosion:	0.0
Eye Irritation:	0.03	Respiratory Toxicity:	0.012
Drug-induced Neurotoxicity:	0.019	Ototoxicity:	0.979
Hematotoxicity:	0.886	Drug-induced Nephrotoxicity:	0.954
Genotoxicity:	0.641	RPMI-8226 Immunitoxicity:	0.555
A549 Cytotoxicity:	0.996	Hek293 Cytotoxicity:	0.79
BCF:	0.247 ? 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:	4.701 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.823 ? 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
NPO51037	Erythroxylum cuneifolium	Species	Erythroxylaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29507	Erythroxylum argentinum	Species	Erythroxylaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29507	Erythroxylum argentinum	Species	Erythroxylaceae	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 NPC533617 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	18834
0.1-0.2	26343
0.2-0.3	3533
0.3-0.4	705
0.4-0.5	322
0.5-0.6	100
0.6-0.7	15
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
0.7113	Intermediate Similarity	NPC473327
0.6436	Remote Similarity	NPC209296
0.6392	Remote Similarity	NPC251417
0.6337	Remote Similarity	NPC470443
0.6286	Remote Similarity	NPC244875
0.6238	Remote Similarity	NPC488073
0.6238	Remote Similarity	NPC126784
0.6238	Remote Similarity	NPC241423
0.6211	Remote Similarity	NPC611303
0.6204	Remote Similarity	NPC480441
0.6139	Remote Similarity	NPC186816
0.6078	Remote Similarity	NPC475366
0.6055	Remote Similarity	NPC25523
0.6	Remote Similarity	NPC476472
0.6	Remote Similarity	NPC294815
0.6	Remote Similarity	NPC16194
0.598	Remote Similarity	NPC473571
0.598	Remote Similarity	NPC110941
0.5979	Remote Similarity	NPC120099
0.5882	Remote Similarity	NPC203259
0.5882	Remote Similarity	NPC33054
0.5882	Remote Similarity	NPC102028
0.5882	Remote Similarity	NPC176740
0.5882	Remote Similarity	NPC471725
0.5882	Remote Similarity	NPC134532
0.5882	Remote Similarity	NPC156869
0.5882	Remote Similarity	NPC602582
0.5859	Remote Similarity	NPC61791
0.5816	Remote Similarity	NPC21666
0.5789	Remote Similarity	NPC198199
0.5784	Remote Similarity	NPC173582
0.5784	Remote Similarity	NPC265885
0.5784	Remote Similarity	NPC181465
0.5784	Remote Similarity	NPC215710
0.5784	Remote Similarity	NPC473438
0.5784	Remote Similarity	NPC253788
0.5728	Remote Similarity	NPC22062
0.5728	Remote Similarity	NPC473634
0.5728	Remote Similarity	NPC138811
0.5714	Remote Similarity	NPC219904
0.5701	Remote Similarity	NPC473073
0.5686	Remote Similarity	NPC295613
0.566	Remote Similarity	NPC606657
0.5641	Remote Similarity	NPC120952
0.5631	Remote Similarity	NPC39834
0.5612	Remote Similarity	NPC599850
0.56	Remote Similarity	NPC605784
0.5577	Remote Similarity	NPC129827
0.5577	Remote Similarity	NPC65563
0.5577	Remote Similarity	NPC470949
0.5575	Remote Similarity	NPC277532
0.5556	Remote Similarity	NPC60735
0.5556	Remote Similarity	NPC26230
0.5545	Remote Similarity	NPC14187
0.5536	Remote Similarity	NPC292019
0.5536	Remote Similarity	NPC202908
0.5524	Remote Similarity	NPC204693
0.55	Remote Similarity	NPC284960
0.55	Remote Similarity	NPC609478
0.5472	Remote Similarity	NPC284277
0.5464	Remote Similarity	NPC289667
0.5463	Remote Similarity	NPC142142
0.5462	Remote Similarity	NPC192539
0.5455	Remote Similarity	NPC135358
0.5446	Remote Similarity	NPC116458
0.5446	Remote Similarity	NPC246943
0.5446	Remote Similarity	NPC189564
0.5385	Remote Similarity	NPC473657
0.5364	Remote Similarity	NPC470445
0.5357	Remote Similarity	NPC203145
0.5354	Remote Similarity	NPC271692
0.5347	Remote Similarity	NPC22832
0.5347	Remote Similarity	NPC486578
0.5333	Remote Similarity	NPC67105
0.5327	Remote Similarity	NPC488074
0.5315	Remote Similarity	NPC470446
0.5315	Remote Similarity	NPC602448
0.53	Remote Similarity	NPC472459
0.53	Remote Similarity	NPC182045
0.5294	Remote Similarity	NPC150442
0.5283	Remote Similarity	NPC473512
0.5283	Remote Similarity	NPC210073
0.5253	Remote Similarity	NPC136042
0.5238	Remote Similarity	NPC187379
0.5227	Remote Similarity	NPC605582
0.52	Remote Similarity	NPC46420
0.52	Remote Similarity	NPC84362
0.5189	Remote Similarity	NPC15358
0.5189	Remote Similarity	NPC44931
0.5189	Remote Similarity	NPC275454
0.5189	Remote Similarity	NPC227508
0.5185	Remote Similarity	NPC240306
0.5185	Remote Similarity	NPC475497
0.5172	Remote Similarity	NPC311850
0.5167	Remote Similarity	NPC488078
0.5149	Remote Similarity	NPC42773
0.5149	Remote Similarity	NPC45522
0.5135	Remote Similarity	NPC470447
0.513	Remote Similarity	NPC173837
0.51	Remote Similarity	NPC297987
0.51	Remote Similarity	NPC64305
0.51	Remote Similarity	NPC158674
0.5098	Remote Similarity	NPC285197
0.5098	Remote Similarity	NPC488071
0.5094	Remote Similarity	NPC236191
0.5094	Remote Similarity	NPC51774
0.5091	Remote Similarity	NPC32641
0.5091	Remote Similarity	NPC256188
0.5091	Remote Similarity	NPC35119
0.5089	Remote Similarity	NPC470449
0.5088	Remote Similarity	NPC89052
0.5054	Remote Similarity	NPC37074
0.505	Remote Similarity	NPC610763
0.5047	Remote Similarity	NPC67326
0.5046	Remote Similarity	NPC153755
0.5042	Remote Similarity	NPC68592

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC533617 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5021
0.1-0.2	4045
0.2-0.3	73
0.3-0.4	4
0.4-0.5	2
0.5-0.6	1
0.6-0.7	3
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
0.703	Intermediate Similarity	NPD7472	Pre-clinical
0.6436	Remote Similarity	NPD7054	Phase 4
0.6154	Remote Similarity	NPD7251	Phase 2
0.6075	Remote Similarity	NPD7808	Phase 3
0.5882	Remote Similarity	NPD6797	Phase 2

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