NPASS Compound

Natural Product: NPC26454

Natural Product ID	NPC26454
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WQGFZONMTGYTJZ-MJRUUCJPSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	102408529
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001511] Lignan glycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 100104 0 0 0 0 0 0 0 0999 V2000 10.1150 -3.0765 0.8604 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8437 -1.8979 0.1527 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5247 -1.4357 0.1000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5020 -2.0956 0.7136 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1622 -1.6632 0.6840 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9256 -0.5091 -0.0183 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9746 0.1707 -0.6477 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2675 -0.2649 -0.6051 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2951 0.4182 -1.2326 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1650 -2.5221 1.2678 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1083 -2.1995 1.9311 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7114 -0.8596 2.2530 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5804 -0.7234 2.8620 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3584 0.3063 2.0220 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9850 1.6055 2.3357 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7584 2.1197 1.6811 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6526 3.6197 1.9001 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5526 4.1579 1.0258 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3128 3.3074 1.1496 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6803 1.8688 0.9303 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4626 1.0503 0.9360 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5102 0.3572 -0.2357 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6887 -0.5260 -0.4568 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0197 0.1575 -0.4818 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2681 1.0691 0.6491 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5967 1.7216 0.5675 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7024 1.1591 1.1414 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9571 1.7669 1.0695 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0419 2.9726 0.3887 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9459 3.5619 -0.1985 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7020 2.9267 -0.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0753 4.7733 -0.8719 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9421 5.3970 -1.4858 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2682 3.6143 0.2910 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0329 1.1628 1.6609 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0087 -0.0421 2.3566 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9267 0.8381 -1.8281 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4486 -0.1882 -2.6328 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6111 -0.9939 -1.9175 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8368 -2.4432 -2.0645 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7907 -3.3498 -2.1585 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9255 -4.6959 -2.3002 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1911 -5.2234 -2.3574 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2800 -4.3844 -2.2709 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1085 -3.0245 -2.1279 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5243 -4.9881 -2.3358 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6700 -4.1646 -2.2498 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3141 -6.6114 -2.5033 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1880 -5.5101 -2.3841 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4670 -4.9374 -2.3238 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5763 1.4701 1.9390 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6303 3.7129 0.1986 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2925 5.4893 1.3462 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8436 4.1781 1.4470 O 0 0 0 0 0 0 0 0 0 0 0 0 9.6758 -3.0254 1.8660 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2167 -3.2091 0.8556 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6328 -3.9262 0.3003 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7235 -3.0166 1.2639 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9419 -0.1073 -0.1863 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7695 1.0806 -1.1935 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2151 0.4565 -0.8344 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3579 -3.6196 1.1060 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4666 -3.0278 2.2746 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8177 2.3250 2.0468 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9494 1.7587 3.4665 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9217 2.0186 0.5657 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5192 3.8813 2.9598 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9103 4.0994 -0.0358 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0847 3.4628 2.1822 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2602 1.7909 -0.0079 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4093 -0.3005 -0.2661 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3390 1.0802 -1.0623 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6610 -1.3980 0.2300 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8164 -0.6110 -0.5094 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5450 1.8844 0.7879 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2384 0.4777 1.5882 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6069 0.2314 1.6593 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8528 3.4058 -0.5776 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2994 5.7392 -0.6242 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2429 6.3180 -2.0177 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3568 4.6896 -2.1039 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7851 3.4470 -0.5696 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1288 -0.1341 3.0006 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0188 -0.8773 1.6012 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9700 -0.1297 2.9162 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1851 1.6538 -1.7878 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8893 1.1967 -2.2031 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5745 -0.8093 -2.3348 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2022 -2.9022 -2.1092 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9626 -2.3717 -2.0689 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8174 -3.5357 -3.1623 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5875 -4.7630 -2.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5170 -3.4758 -1.3969 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8754 -7.2582 -1.8741 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7008 -4.2897 -3.1738 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5873 -4.3312 -1.3879 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2518 -5.7315 -2.2662 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7203 4.6975 0.2084 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4337 6.0547 0.5465 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7487 4.4790 0.5010 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 5 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 32 33 1 0 29 34 1 0 28 35 1 0 35 36 1 0 24 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 2 0 41 42 1 0 42 43 2 0 43 44 1 0 44 45 2 0 44 46 1 0 46 47 1 0 43 48 1 0 42 49 1 0 49 50 1 0 20 51 1 0 19 52 1 0 18 53 1 0 17 54 1 0 8 3 1 0 51 16 1 0 39 23 1 0 45 40 1 0 31 26 1 0 1 55 1 0 1 56 1 0 1 57 1 0 4 58 1 0 6 59 1 0 7 60 1 0 9 61 1 0 10 62 1 0 11 63 1 0 15 64 1 0 15 65 1 0 16 66 1 6 17 67 1 1 18 68 1 6 19 69 1 1 20 70 1 6 22 71 1 0 22 72 1 0 23 73 1 1 24 74 1 6 25 75 1 0 25 76 1 0 27 77 1 0 31 78 1 0 33 79 1 0 33 80 1 0 33 81 1 0 34 82 1 0 36 83 1 0 36 84 1 0 36 85 1 0 37 86 1 0 37 87 1 0 39 88 1 6 41 89 1 0 45 90 1 0 47 91 1 0 47 92 1 0 47 93 1 0 48 94 1 0 50 95 1 0 50 96 1 0 50 97 1 0 52 98 1 0 53 99 1 0 54100 1 0 M END

Standard InCHIKey	WQGFZONMTGYTJZ-MJRUUCJPSA-N
Standard InCHI	InChI=1S/C38H46O16/c1-46-25-11-19(6-8-24(25)39)7-9-31(40)51-18-30-34(43)35(44)36(45)38(54-30)53-17-23-22(10-20-12-26(47-2)32(41)27(13-20)48-3)16-52-37(23)21-14-28(49-4)33(42)29(15-21)50-5/h6-9,11-15,22-23,30,34-39,41-45H,10,16-18H2,1-5H3/b9-7-/t22-,23-,30+,34+,35-,36+,37+,38+/m0/s1
SMILES	COc1cc(ccc1O)/C=CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@H](OC[C@H]2[C@@H](Cc3cc(c(c(c3)OC)O)OC)CO[C@@H]2c2cc(c(c(c2)OC)O)OC)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	758.28	Volume:	734.664 ? Van der Waals volume.
Dense:	1.032	LogP:	1.483 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.773 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.397 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	31.0
TPSA:	221.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.097	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.858	Fsp³:	0.447
MCE-18:	116.455 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.811	Fluc inhibitor:	0.69 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.085 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.621 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.064	Promiscuous compounds:	0.208

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.056	MDCK Permeability:	-5.396
Pgp-inhibitor:	0.841	Pgp-substrate:	0.031
PAMPA:	0.001 ? 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):	0.038
20% Bioavailability (F20%):	0.29	30% Bioavailability (F30%):	0.381
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.915
Plasma Protein Binding (PPB):	91.197%	Volume Distribution (VD):	-0.374
Fu:	10.683% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.438
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.019	CYP1A2-substrate:	0.557
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.451
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.191
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.314
CYP3A4-inhibitor:	0.443	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.816 ? 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):

2.655

Half-life (T1/2):

3.22

ADMET: Toxicity

hERG Blockers:	0.142	hERG Blockers (10um):	0.544
Human Hepatotoxicity (H-HT):	0.685	Drug-induced Liver Injury (DILI):	0.52
AMES Toxicity:	0.405	Rat Oral Acute Toxicity:	0.028
Maximum Recommended Daily Dose:	0.226	Skin Sensitization:	1.0
Carcinogencity:	0.022	Eye Corrosion:	0.0
Eye Irritation:	0.218	Respiratory Toxicity:	0.05
Drug-induced Neurotoxicity:	0.055	Ototoxicity:	0.717
Hematotoxicity:	0.028	Drug-induced Nephrotoxicity:	0.87
Genotoxicity:	0.06	RPMI-8226 Immunitoxicity:	0.449
A549 Cytotoxicity:	0.901	Hek293 Cytotoxicity:	0.707
BCF:	0.93 ? 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:	3.92 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.144 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.654 ? 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
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252914]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19251412]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37375900]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9165	Asclepias curassavica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3369	Anemone narcissiflora	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2175	Hyperbaena columbica	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8349	Uga sinensis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO26375	Viburnum grandifolium	Species	Adoxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9165	Asclepias curassavica	Species	Apocynaceae	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 NPC26454 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	15279
0.1-0.2	29875
0.2-0.3	3763
0.3-0.4	737
0.4-0.5	160
0.5-0.6	35
0.6-0.7	5
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
0.7284	Intermediate Similarity	NPC252402
0.7284	Intermediate Similarity	NPC102934
0.6559	Remote Similarity	NPC11411
0.6437	Remote Similarity	NPC472711
0.6429	Remote Similarity	NPC472713
0.6429	Remote Similarity	NPC606627
0.6061	Remote Similarity	NPC59516
0.5914	Remote Similarity	NPC226005
0.5909	Remote Similarity	NPC67467
0.5644	Remote Similarity	NPC472611
0.5625	Remote Similarity	NPC186073
0.56	Remote Similarity	NPC125823
0.56	Remote Similarity	NPC7145
0.56	Remote Similarity	NPC143480
0.5567	Remote Similarity	NPC476865
0.5556	Remote Similarity	NPC300262
0.5545	Remote Similarity	NPC149873
0.551	Remote Similarity	NPC83743
0.5437	Remote Similarity	NPC201148
0.5422	Remote Similarity	NPC110699
0.5422	Remote Similarity	NPC106055
0.5392	Remote Similarity	NPC7191
0.5368	Remote Similarity	NPC471405
0.5361	Remote Similarity	NPC21516
0.534	Remote Similarity	NPC600370
0.5312	Remote Similarity	NPC472612
0.5278	Remote Similarity	NPC479771
0.5258	Remote Similarity	NPC476869
0.5253	Remote Similarity	NPC262182
0.5204	Remote Similarity	NPC476868
0.5172	Remote Similarity	NPC278961
0.5172	Remote Similarity	NPC113680
0.5116	Remote Similarity	NPC67247
0.5111	Remote Similarity	NPC288416
0.5104	Remote Similarity	NPC291296
0.5096	Remote Similarity	NPC3460
0.5057	Remote Similarity	NPC157554
0.5056	Remote Similarity	NPC120852
0.5051	Remote Similarity	NPC90896
0.505	Remote Similarity	NPC479767
0.5048	Remote Similarity	NPC481006
0.5043	Remote Similarity	NPC286809

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC26454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4707
0.1-0.2	4343
0.2-0.3	95
0.3-0.4	4
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
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
		NPD

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