NPASS Compound

Natural Product: NPC575890

Natural Product ID	NPC575890
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-methoxy-phenyl)-7-[(2~{S},3~{S},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-7-[(2~{S},3~{S},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)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 98103 0 0 0 0 0 0 0 0999 V2000 3.5543 2.4083 -5.2779 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3789 2.0292 -5.9163 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4154 1.2825 -5.2566 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6442 0.9188 -3.9438 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6863 0.1653 -3.2577 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0411 -0.2538 -1.8909 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1255 -0.6838 -1.0018 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2409 -0.7635 -1.2318 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1099 0.2403 -0.7313 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7601 -0.3742 0.4165 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1923 0.5979 1.2879 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9939 0.0916 2.4479 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0723 -0.6471 2.2776 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1981 -0.3596 1.6380 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.3312 -0.3765 2.5039 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.3596 0.2410 1.8072 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.5184 0.6074 2.7056 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4951 1.2204 1.9121 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8534 -0.5885 0.6447 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.7146 0.2361 -0.1048 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6544 -0.8746 -0.2536 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.9971 -1.7118 -1.3113 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5493 -1.4438 0.6009 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4456 -1.7876 -0.1683 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6743 1.8452 0.6762 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7975 2.9295 1.0086 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9537 1.8104 -0.7710 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3008 1.8618 -1.1183 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2166 0.7146 -1.5506 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9357 1.1873 -2.8284 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6021 -1.0668 0.2707 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2458 -1.4679 1.0890 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9347 -0.9911 0.5639 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4393 -1.3547 1.7926 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5354 -1.8083 2.7448 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7933 -1.2710 2.0693 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6997 -0.8166 1.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0610 -0.7143 1.3336 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7831 -1.0307 2.4694 C 0 0 2 0 0 0 0 0 0 0 0 0 7.4602 0.0492 2.9963 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6961 0.3068 2.5007 C 0 0 1 0 0 0 0 0 0 0 0 0 9.8049 0.0976 3.5211 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6024 0.9464 4.6119 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0848 -0.3658 1.2286 C 0 0 1 0 0 0 0 0 0 0 0 0 10.4498 -0.1677 0.9750 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7931 -1.8348 1.2275 C 0 0 2 0 0 0 0 0 0 0 0 0 8.4079 -2.2124 -0.0697 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7317 -2.2030 2.2361 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0462 -3.2886 1.7166 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1607 -0.4615 -0.0972 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8211 -0.5353 -0.3967 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3350 -0.1984 -1.5476 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4510 -0.1905 -3.9112 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6443 0.1967 -5.2359 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2741 0.9400 -5.9474 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0370 1.3023 -7.2656 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3528 2.8817 -4.2928 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0622 3.1449 -5.9439 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2430 1.5492 -5.1052 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5547 1.2017 -3.4223 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4804 1.0532 -0.3272 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1888 0.9037 1.8050 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2223 0.9993 3.0935 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2526 -0.4889 3.1158 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2963 0.6021 1.1123 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9647 1.1864 1.3809 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1719 1.3634 3.4309 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9443 -0.2510 3.2536 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3226 2.2006 1.8273 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4068 -1.4879 0.9299 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6355 -0.1221 -0.1456 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3269 0.1154 -0.6226 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9850 -1.8579 -1.3383 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9640 -2.3193 1.1489 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6905 -1.6545 -1.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6204 2.1661 1.2128 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5747 2.7277 1.9737 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5292 2.7698 -1.2088 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3489 1.8126 -2.1077 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9325 -0.1479 -1.7336 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1733 1.8446 -2.7597 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5476 -1.2929 3.6299 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1325 -1.5682 3.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0499 -1.3323 3.2790 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7314 1.4209 2.2897 H 0 0 0 0 0 0 0 0 0 0 0 0 10.7558 0.4063 3.0287 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9346 -0.9437 3.8273 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4262 1.4102 4.8391 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5699 0.0852 0.3306 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9782 -0.9189 1.3484 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7352 -2.3796 1.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7809 -1.5508 -0.7051 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2108 -2.4442 3.1950 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6545 -2.9981 0.8576 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8220 -0.0969 -0.8831 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2007 -0.7923 -3.4133 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5560 -0.0932 -5.7373 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4466 0.6086 -7.8348 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 17 18 1 0 16 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 11 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 7 31 1 0 31 32 2 0 31 33 1 0 33 34 2 0 34 35 1 0 34 36 1 0 36 37 2 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 41 44 1 0 44 45 1 0 44 46 1 0 46 47 1 0 46 48 1 0 48 49 1 0 37 50 1 0 50 51 2 0 51 52 1 0 5 53 2 0 53 54 1 0 54 55 2 0 55 56 1 0 55 3 1 0 52 6 1 0 29 9 1 0 51 33 1 0 23 14 1 0 48 39 1 0 1 57 1 0 1 58 1 0 1 59 1 0 4 60 1 0 9 61 1 1 11 62 1 1 12 63 1 0 12 64 1 0 14 65 1 6 16 66 1 6 17 67 1 0 17 68 1 0 18 69 1 0 19 70 1 1 20 71 1 0 21 72 1 6 22 73 1 0 23 74 1 1 24 75 1 0 25 76 1 1 26 77 1 0 27 78 1 6 28 79 1 0 29 80 1 6 30 81 1 0 35 82 1 0 36 83 1 0 39 84 1 1 41 85 1 6 42 86 1 0 42 87 1 0 43 88 1 0 44 89 1 6 45 90 1 0 46 91 1 1 47 92 1 0 48 93 1 1 49 94 1 0 50 95 1 0 53 96 1 0 54 97 1 0 56 98 1 0 M END

Standard InCHIKey	LQPFCZMAURITGZ-NUMGFLMXSA-N
Standard InCHI	InChI=1S/C34H42O22/c1-49-14-4-10(2-3-12(14)37)30-31(23(42)19-13(38)5-11(6-15(19)52-30)51-33-28(47)25(44)21(40)17(8-36)54-33)56-34-29(48)26(45)22(41)18(55-34)9-50-32-27(46)24(43)20(39)16(7-35)53-32/h2-6,16-18,20-22,24-29,32-41,43-48H,7-9H2,1H3/t16-,17+,18-,20-,21-,22-,24+,25+,26+,27-,28+,29-,32-,33-,34+/m1/s1
SMILES	COC1=CC(C2=C(O[C@@H]3O[C@H](CO[C@@H]4O[C@H](CO)[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=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	802.22	Volume:	717.575 ? Van der Waals volume.
Dense:	1.118	LogP:	-1.028 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.316 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.613 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	36.0
TPSA:	357.81 ? 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:	0.086	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.392	Fsp³:	0.559
MCE-18:	153.34 ? 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:	0.638	Fluc inhibitor:	0.29 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.773 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.638 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.127	Promiscuous compounds:	0.533

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.928	MDCK Permeability:	-4.908
Pgp-inhibitor:	0.0	Pgp-substrate:	0.866
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%):	0.699	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.04
Plasma Protein Binding (PPB):	75.902%	Volume Distribution (VD):	-0.189
Fu:	22.946% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.186
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:	0.26
HLM stability:	0.001 ? 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):

0.944

Half-life (T1/2):

5.51

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.011
Human Hepatotoxicity (H-HT):	0.713	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.99	Rat Oral Acute Toxicity:	0.001
Maximum Recommended Daily Dose:	0.001	Skin Sensitization:	1.0
Carcinogencity:	0.022	Eye Corrosion:	0.0
Eye Irritation:	0.002	Respiratory Toxicity:	0.0
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.999
Hematotoxicity:	0.359	Drug-induced Nephrotoxicity:	0.952
Genotoxicity:	0.637	RPMI-8226 Immunitoxicity:	0.309
A549 Cytotoxicity:	0.857	Hek293 Cytotoxicity:	0.347
BCF:	0.299 ? 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:	2.727 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.44 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.447 ? 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
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[11141122]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO54831	Tribulus pentandrus	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	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 NPC575890 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	24316
0.1-0.2	21418
0.2-0.3	2908
0.3-0.4	676
0.4-0.5	317
0.5-0.6	154
0.6-0.7	40
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	Natural Product ID
0.7204	Intermediate Similarity	NPC186816
0.7188	Intermediate Similarity	NPC476472
0.7188	Intermediate Similarity	NPC294815
0.7188	Intermediate Similarity	NPC16194
0.7011	Intermediate Similarity	NPC297987
0.7011	Intermediate Similarity	NPC136042
0.6947	Remote Similarity	NPC488073
0.6932	Remote Similarity	NPC84362
0.6923	Remote Similarity	NPC203050
0.6923	Remote Similarity	NPC488072
0.6923	Remote Similarity	NPC225434
0.6863	Remote Similarity	NPC480441
0.6863	Remote Similarity	NPC25523
0.6813	Remote Similarity	NPC311830
0.6737	Remote Similarity	NPC156869
0.6705	Remote Similarity	NPC289667
0.6703	Remote Similarity	NPC101026
0.6703	Remote Similarity	NPC488077
0.6635	Remote Similarity	NPC277532
0.663	Remote Similarity	NPC116458
0.663	Remote Similarity	NPC246943
0.663	Remote Similarity	NPC605784
0.6598	Remote Similarity	NPC153755
0.6559	Remote Similarity	NPC601586
0.6458	Remote Similarity	NPC275454
0.6422	Remote Similarity	NPC488079
0.6421	Remote Similarity	NPC251417
0.6408	Remote Similarity	NPC121703
0.6364	Remote Similarity	NPC470443
0.6344	Remote Similarity	NPC601144
0.6277	Remote Similarity	NPC206123
0.6196	Remote Similarity	NPC46420
0.6196	Remote Similarity	NPC271692
0.6161	Remote Similarity	NPC192539
0.6154	Remote Similarity	NPC14187
0.6139	Remote Similarity	NPC209296
0.6122	Remote Similarity	NPC67105
0.61	Remote Similarity	NPC126784
0.61	Remote Similarity	NPC241423
0.61	Remote Similarity	NPC64425
0.6078	Remote Similarity	NPC142142
0.6078	Remote Similarity	NPC486577
0.6064	Remote Similarity	NPC611303
0.6061	Remote Similarity	NPC210073
0.6	Remote Similarity	NPC473571
0.6	Remote Similarity	NPC110941
0.5982	Remote Similarity	NPC470720
0.5981	Remote Similarity	NPC219043
0.598	Remote Similarity	NPC35119
0.598	Remote Similarity	NPC473327
0.5978	Remote Similarity	NPC249281
0.596	Remote Similarity	NPC173582
0.596	Remote Similarity	NPC44931
0.596	Remote Similarity	NPC265885
0.596	Remote Similarity	NPC181465
0.596	Remote Similarity	NPC215710
0.596	Remote Similarity	NPC473438
0.596	Remote Similarity	NPC253788
0.5943	Remote Similarity	NPC89052
0.5941	Remote Similarity	NPC488074
0.5938	Remote Similarity	NPC223747
0.5926	Remote Similarity	NPC217520
0.5914	Remote Similarity	NPC277205
0.5914	Remote Similarity	NPC37919
0.59	Remote Similarity	NPC22062
0.59	Remote Similarity	NPC203259
0.59	Remote Similarity	NPC479405
0.59	Remote Similarity	NPC473634
0.59	Remote Similarity	NPC33054
0.59	Remote Similarity	NPC176740
0.59	Remote Similarity	NPC471725
0.59	Remote Similarity	NPC134532
0.59	Remote Similarity	NPC138811
0.59	Remote Similarity	NPC602582
0.5895	Remote Similarity	NPC488071
0.5893	Remote Similarity	NPC470717
0.5888	Remote Similarity	NPC189564
0.5876	Remote Similarity	NPC276377
0.5859	Remote Similarity	NPC471079
0.5856	Remote Similarity	NPC295625
0.5851	Remote Similarity	NPC24043
0.5842	Remote Similarity	NPC479404
0.5841	Remote Similarity	NPC488078
0.5833	Remote Similarity	NPC22832
0.5833	Remote Similarity	NPC292019
0.5833	Remote Similarity	NPC202908
0.5833	Remote Similarity	NPC78326
0.5833	Remote Similarity	NPC173837
0.5833	Remote Similarity	NPC486578
0.5825	Remote Similarity	NPC32641
0.5825	Remote Similarity	NPC256188
0.5818	Remote Similarity	NPC139571
0.58	Remote Similarity	NPC67326
0.5789	Remote Similarity	NPC42773
0.5789	Remote Similarity	NPC45522
0.5789	Remote Similarity	NPC325555
0.5789	Remote Similarity	NPC226304
0.5784	Remote Similarity	NPC240306
0.5755	Remote Similarity	NPC135358
0.5752	Remote Similarity	NPC470719
0.5745	Remote Similarity	NPC158674
0.5745	Remote Similarity	NPC323593
0.5745	Remote Similarity	NPC203500
0.5745	Remote Similarity	NPC189142
0.5745	Remote Similarity	NPC77660
0.5743	Remote Similarity	NPC150164
0.5729	Remote Similarity	NPC285197
0.5728	Remote Similarity	NPC65711
0.5728	Remote Similarity	NPC479403
0.5714	Remote Similarity	NPC473073
0.5684	Remote Similarity	NPC488080
0.5684	Remote Similarity	NPC169977
0.567	Remote Similarity	NPC120099
0.5644	Remote Similarity	NPC227508
0.5638	Remote Similarity	NPC39360
0.5638	Remote Similarity	NPC77672
0.5638	Remote Similarity	NPC133671
0.5638	Remote Similarity	NPC135391
0.5638	Remote Similarity	NPC29763
0.5638	Remote Similarity	NPC78263
0.5638	Remote Similarity	NPC210003
0.5638	Remote Similarity	NPC250069
0.5636	Remote Similarity	NPC164704
0.5625	Remote Similarity	NPC472459
0.5612	Remote Similarity	NPC602805
0.5607	Remote Similarity	NPC470446
0.5588	Remote Similarity	NPC65563
0.5588	Remote Similarity	NPC470949
0.5579	Remote Similarity	NPC145038
0.5579	Remote Similarity	NPC56077
0.5579	Remote Similarity	NPC281131
0.5579	Remote Similarity	NPC95090
0.5579	Remote Similarity	NPC253662
0.5579	Remote Similarity	NPC179950
0.5579	Remote Similarity	NPC27408
0.5579	Remote Similarity	NPC88789
0.5579	Remote Similarity	NPC491374
0.5566	Remote Similarity	NPC195257
0.5566	Remote Similarity	NPC220173
0.5545	Remote Similarity	NPC609888
0.5536	Remote Similarity	NPC470716
0.5524	Remote Similarity	NPC473623
0.5524	Remote Similarity	NPC606657
0.5521	Remote Similarity	NPC603655
0.5514	Remote Similarity	NPC470449
0.551	Remote Similarity	NPC243930
0.551	Remote Similarity	NPC21666
0.5505	Remote Similarity	NPC203145
0.5495	Remote Similarity	NPC470715
0.549	Remote Similarity	NPC39834
0.5472	Remote Similarity	NPC488089
0.5464	Remote Similarity	NPC599850
0.5455	Remote Similarity	NPC607707
0.5437	Remote Similarity	NPC102028
0.5417	Remote Similarity	NPC64305
0.5408	Remote Similarity	NPC60735
0.5408	Remote Similarity	NPC26230
0.54	Remote Similarity	NPC469931
0.5393	Remote Similarity	NPC37074
0.5392	Remote Similarity	NPC480466
0.5391	Remote Similarity	NPC198199
0.5385	Remote Similarity	NPC209550
0.5377	Remote Similarity	NPC229409
0.5377	Remote Similarity	NPC72016
0.537	Remote Similarity	NPC292929
0.5354	Remote Similarity	NPC609478
0.5347	Remote Similarity	NPC116864
0.5347	Remote Similarity	NPC244776
0.5333	Remote Similarity	NPC46202
0.5333	Remote Similarity	NPC287780
0.5333	Remote Similarity	NPC60982
0.5333	Remote Similarity	NPC64051
0.5321	Remote Similarity	NPC602448
0.5315	Remote Similarity	NPC473072
0.5312	Remote Similarity	NPC261866
0.5268	Remote Similarity	NPC48984
0.5268	Remote Similarity	NPC480796
0.5268	Remote Similarity	NPC472993
0.5258	Remote Similarity	NPC8573
0.5254	Remote Similarity	NPC120952
0.5254	Remote Similarity	NPC138990
0.5253	Remote Similarity	NPC307938
0.5229	Remote Similarity	NPC101636
0.5229	Remote Similarity	NPC470445
0.521	Remote Similarity	NPC175429
0.52	Remote Similarity	NPC197285
0.5175	Remote Similarity	NPC311850
0.5161	Remote Similarity	NPC223860
0.5155	Remote Similarity	NPC19388
0.5155	Remote Similarity	NPC240431
0.5155	Remote Similarity	NPC55786
0.5143	Remote Similarity	NPC303913
0.5138	Remote Similarity	NPC470447
0.5138	Remote Similarity	NPC76831
0.5133	Remote Similarity	NPC477895
0.513	Remote Similarity	NPC488083
0.5096	Remote Similarity	NPC29958
0.5096	Remote Similarity	NPC139320
0.5051	Remote Similarity	NPC22195
0.5051	Remote Similarity	NPC27640

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC575890 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5936
0.1-0.2	3153
0.2-0.3	50
0.3-0.4	5
0.4-0.5	2
0.5-0.6	1
0.6-0.7	3
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
0.6837	Remote Similarity	NPD7251	Phase 2
0.6569	Remote Similarity	NPD7808	Phase 3
0.6139	Remote Similarity	NPD7054	Phase 4
0.59	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