NPASS Compound

Natural Product: NPC162524

Natural Product ID	NPC162524
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WCRGITKUZAHUSZ-XIFFEERXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0000054] Benzylisoquinolines

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 84 89 0 0 0 0 0 0 0 0999 V2000 -5.4042 -2.2636 0.6379 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4211 -1.1972 0.7161 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5382 -0.5668 2.0034 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2227 0.7547 2.0147 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3541 0.7258 1.0495 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6038 1.1838 1.3568 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5877 1.1177 0.3861 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2812 0.5875 -0.8753 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0237 0.1250 -1.1873 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0530 0.1961 -0.2150 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6642 -0.2372 -0.3549 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2621 -0.7793 -1.6831 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8114 -1.0931 -1.6580 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9416 -0.1014 -2.0860 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5589 -0.3262 -2.0618 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0695 -1.5339 -1.6121 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9572 -2.4879 -1.1990 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3274 -2.2970 -1.2104 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3190 -1.7343 -1.5967 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0512 -1.1192 -0.5755 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0855 -0.2381 -0.8779 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8458 0.4072 0.0660 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5207 0.1281 1.3964 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5170 -0.7277 1.7567 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7738 -1.3588 0.7499 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7615 -2.2219 1.1445 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4797 -2.4629 2.4980 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9581 1.3274 -0.2360 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2455 0.5737 -0.0155 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2574 -0.6273 0.4054 N 0 0 0 0 0 0 0 0 0 0 0 0 7.3717 -1.4675 0.6607 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7135 -0.8435 0.5689 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6921 0.5054 0.0074 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9123 1.1237 -0.2566 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9552 2.4044 -0.7518 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7789 3.0726 -0.9857 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5536 2.4943 -0.7376 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5401 1.2063 -0.2407 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1991 2.9718 -0.9966 O 0 0 0 0 0 0 0 0 0 0 0 0 12.3784 2.2452 -0.7403 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3191 0.5583 -1.7845 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.1534 0.0391 -3.0726 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8521 1.5709 0.6617 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1599 2.0993 1.9152 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2393 -1.9848 1.3130 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8667 -2.3328 -0.3771 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0145 -3.2427 0.9143 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0179 -1.2262 2.7501 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5046 -0.3894 2.4424 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6168 0.9287 3.0340 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5274 1.6054 1.7811 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8021 1.5842 2.3433 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7657 -0.2844 -2.1458 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0123 0.6348 -0.1323 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4275 -0.0010 -2.4530 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7862 -1.6898 -1.9911 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2576 0.8521 -2.4436 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1096 0.4421 -2.3937 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6133 -3.4422 -0.8521 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0434 -3.0399 -0.8871 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2892 -0.0619 -1.9167 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0902 0.6128 2.1740 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2536 -0.9543 2.7787 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1426 -1.4724 2.9222 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4303 -3.1325 2.5191 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3185 -2.8932 3.0558 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9690 2.1741 0.4849 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9566 1.6715 -1.2723 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3305 -2.3335 -0.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2618 -1.8902 1.7045 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3858 -1.5319 -0.0346 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2011 -0.8418 1.5909 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8370 0.6041 -0.0768 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8538 4.0853 -1.3792 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6181 3.0270 -0.9235 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2911 2.8466 -0.9511 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3991 1.3817 -1.4414 H 0 0 0 0 0 0 0 0 0 0 0 0 12.3530 1.9391 0.3318 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9877 0.3679 -3.7514 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0918 -1.0744 -2.9923 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2173 0.4526 -3.5549 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2673 1.3386 2.7209 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1137 2.7005 1.9043 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4006 2.8367 2.2916 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 22 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 35 39 1 0 39 40 1 0 8 41 1 0 41 42 1 0 7 43 1 0 43 44 1 0 11 2 1 0 18 13 1 0 25 20 1 0 38 29 1 0 10 5 1 0 38 33 1 0 1 45 1 0 1 46 1 0 1 47 1 0 3 48 1 0 3 49 1 0 4 50 1 0 4 51 1 0 6 52 1 0 9 53 1 0 11 54 1 1 12 55 1 0 12 56 1 0 14 57 1 0 15 58 1 0 17 59 1 0 18 60 1 0 21 61 1 0 23 62 1 0 24 63 1 0 27 64 1 0 27 65 1 0 27 66 1 0 28 67 1 0 28 68 1 0 31 69 1 0 31 70 1 0 32 71 1 0 32 72 1 0 34 73 1 0 36 74 1 0 37 75 1 0 40 76 1 0 40 77 1 0 40 78 1 0 42 79 1 0 42 80 1 0 42 81 1 0 44 82 1 0 44 83 1 0 44 84 1 0 M END

Standard InCHIKey	WCRGITKUZAHUSZ-XIFFEERXSA-N
Standard InCHI	InChI=1S/C37H40N2O5/c1-39-17-15-27-22-35(42-4)36(43-5)23-31(27)33(39)19-24-6-9-28(10-7-24)44-37-20-25(8-13-34(37)41-3)18-32-30-12-11-29(40-2)21-26(30)14-16-38-32/h6-13,20-23,33H,14-19H2,1-5H3/t33-/m0/s1
SMILES	CN1CCc2cc(c(cc2[C@@H]1Cc1ccc(cc1)Oc1cc(ccc1OC)CC1=NCCc2cc(ccc12)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.29	Volume:	628.84 ? Van der Waals volume.
Dense:	0.942	LogP:	4.27 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.753 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.778 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	34.0
TPSA:	61.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.2	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.313	Fsp³:	0.324
MCE-18:	105.735 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.422 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.525 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.921 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.271

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.688	MDCK Permeability:	-4.585
Pgp-inhibitor:	1.0	Pgp-substrate:	0.072
PAMPA:	0.0 ? 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):	0.001
20% Bioavailability (F20%):	0.096	30% Bioavailability (F30%):	0.008
50% Bioavailability (F50%):	0.717

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.286	MRP1:	0.85
Plasma Protein Binding (PPB):	79.703%	Volume Distribution (VD):	0.233
Fu:	19.021% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.799
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.91
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.428
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.974
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.024
CYP2B6-substrate:	0.986	CYP2C8-inhibitor:	0.983
HLM stability:	0.999 ? 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):

10.91

Half-life (T1/2):

2.067

ADMET: Toxicity

hERG Blockers:	0.939	hERG Blockers (10um):	0.883
Human Hepatotoxicity (H-HT):	0.845	Drug-induced Liver Injury (DILI):	0.491
AMES Toxicity:	0.502	Rat Oral Acute Toxicity:	0.631
Maximum Recommended Daily Dose:	0.984	Skin Sensitization:	0.223
Carcinogencity:	0.341	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.894
Drug-induced Neurotoxicity:	0.99	Ototoxicity:	0.879
Hematotoxicity:	0.377	Drug-induced Nephrotoxicity:	0.564
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.153	Hek293 Cytotoxicity:	0.871
BCF:	2.432 ? 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:	4.993 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.155 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.659 ? 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
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21123068]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28522265]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29641206]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1516	Passiflora suberosa	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7389	Rhodiola atuntsuensis	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5156	Hypoestes rosea	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7389	Rhodiola atuntsuensis	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6730	Crossopteryx febrifuga	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5156	Hypoestes rosea	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1516	Passiflora suberosa	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19931	Pyrus x nivalis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	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 NPC162524 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	33529
0.1-0.2	15581
0.2-0.3	517
0.3-0.4	118
0.4-0.5	64
0.5-0.6	45
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	Natural Product ID
0.7042	Intermediate Similarity	NPC247639
0.7042	Intermediate Similarity	NPC25084
0.6988	Remote Similarity	NPC195538
0.6824	Remote Similarity	NPC249996
0.6098	Remote Similarity	NPC603603
0.5976	Remote Similarity	NPC276890
0.5957	Remote Similarity	NPC41122
0.5957	Remote Similarity	NPC318805
0.5857	Remote Similarity	NPC314682
0.5854	Remote Similarity	NPC76682
0.5854	Remote Similarity	NPC10908
0.5854	Remote Similarity	NPC63646
0.5854	Remote Similarity	NPC317145
0.5854	Remote Similarity	NPC198498
0.5854	Remote Similarity	NPC115284
0.5647	Remote Similarity	NPC12424
0.5647	Remote Similarity	NPC129518
0.5647	Remote Similarity	NPC251580
0.5625	Remote Similarity	NPC85381
0.5581	Remote Similarity	NPC603853
0.5568	Remote Similarity	NPC475393
0.5529	Remote Similarity	NPC227060
0.5517	Remote Similarity	NPC290582
0.5517	Remote Similarity	NPC217748
0.5517	Remote Similarity	NPC73492
0.5517	Remote Similarity	NPC182052
0.5517	Remote Similarity	NPC271013
0.5517	Remote Similarity	NPC299990
0.5517	Remote Similarity	NPC42663
0.5517	Remote Similarity	NPC15414
0.5455	Remote Similarity	NPC279228
0.5393	Remote Similarity	NPC311973
0.5366	Remote Similarity	NPC317272
0.5366	Remote Similarity	NPC268503
0.5357	Remote Similarity	NPC256012
0.5357	Remote Similarity	NPC610965
0.5342	Remote Similarity	NPC213206
0.5342	Remote Similarity	NPC188163
0.5342	Remote Similarity	NPC328750
0.5341	Remote Similarity	NPC480587
0.5333	Remote Similarity	NPC254441
0.5333	Remote Similarity	NPC116465
0.5301	Remote Similarity	NPC30779
0.5222	Remote Similarity	NPC286119
0.5222	Remote Similarity	NPC239824
0.5106	Remote Similarity	NPC243454
0.51	Remote Similarity	NPC234318
0.5057	Remote Similarity	NPC41376
0.5055	Remote Similarity	NPC112248
0.505	Remote Similarity	NPC608576

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC162524 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4670
0.1-0.2	4306
0.2-0.3	161
0.3-0.4	7
0.4-0.5	2
0.5-0.6	4
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
0.5854	Remote Similarity	NPD8099	Discontinued
0.5765	Remote Similarity	NPD8156	Discontinued
0.5517	Remote Similarity	NPD8095	Phase 1
0.5342	Remote Similarity	NPD4664	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