NPASS Compound

Natural Product: NPC471506

Natural Product ID	NPC471506
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6-Deoxymanzamine X
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL253548
PubChem CID	44445400
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001140] Harmala alkaloids

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 86 94 0 0 0 0 0 0 0 0999 V2000 -3.8056 -2.5043 -1.9807 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7799 -2.0152 -2.6250 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3912 -2.3701 -2.4747 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3456 -1.3626 -2.3510 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2375 -0.2431 -1.4455 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1569 0.0064 -0.9427 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6025 -0.3074 0.2552 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4792 -0.9384 1.0669 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8068 -1.3574 2.4281 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3703 -2.2535 2.8951 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6354 -1.7870 2.4481 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3592 -2.6761 1.6158 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7728 -2.2836 1.2765 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3573 -3.2904 0.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7731 -3.5380 -0.9614 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6743 -0.4163 2.0783 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6874 -0.0276 1.0042 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2708 1.4154 1.1709 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4162 2.1886 0.4921 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3811 2.6412 1.5679 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5146 4.1610 1.3925 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9799 4.2892 -0.0355 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1302 4.0343 -0.9501 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7545 3.0041 -1.9596 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8060 1.6033 -1.4081 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8931 1.2868 -0.4261 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2795 0.0143 -0.3953 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9619 3.3448 -0.1227 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8936 -0.1959 0.8231 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0696 0.0009 0.1571 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2681 0.2156 0.8689 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2579 0.2264 2.2466 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0661 0.0241 2.9001 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9884 -0.1691 2.1886 N 0 0 0 0 0 0 0 0 0 0 0 0 6.2581 0.3534 -0.0812 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6127 0.5815 0.0600 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3922 0.6787 -1.0780 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8500 0.5538 -2.3402 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4801 0.3233 -2.4784 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7166 0.2288 -1.3352 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3829 0.0144 -1.1294 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.4346 0.9087 -2.3161 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8190 -2.0964 -2.2276 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0298 -1.2305 -3.3768 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2116 -3.1212 -1.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1267 -3.0008 -3.3967 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1482 -1.0124 -3.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6816 -1.9381 -2.2300 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8197 0.5092 -1.6126 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3183 -1.8886 0.4719 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8894 -0.5877 3.2048 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7205 -2.0237 2.3999 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1541 -3.2521 2.4270 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2675 -2.3876 3.9734 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4170 -3.7052 2.0668 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8537 -2.7038 0.6359 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3913 -2.1365 2.1981 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7771 -1.3124 0.7740 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4700 -3.1383 0.2102 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3304 -4.2789 0.9362 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4499 -4.3619 -1.4010 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8015 -4.1005 -0.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3102 0.1299 3.0135 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7086 -0.1054 1.8783 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2071 1.7039 2.2448 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6097 1.6307 0.5991 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3567 2.1549 1.4105 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9738 2.5117 2.5917 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5653 4.4592 1.4538 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8317 4.7041 2.0529 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5086 5.2797 -0.1630 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0428 3.6535 -0.4136 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4395 4.9848 -1.4146 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8141 3.2822 -2.4229 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5328 3.0410 -2.7780 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7686 0.9058 -2.2765 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8557 1.4766 -1.0037 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0697 -0.7220 -0.5831 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1603 0.3891 2.8018 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9860 0.0187 3.9857 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0055 0.6741 1.0506 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4468 0.8574 -0.9278 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4667 0.6311 -3.2259 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0119 0.2189 -3.4431 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7557 -0.1362 -1.9212 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0911 1.6604 -2.0077 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 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 11 16 1 0 16 17 1 0 17 18 1 1 19 18 1 1 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 1 0 22 28 1 0 7 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 31 35 1 0 35 36 2 0 36 37 1 0 37 38 2 0 38 39 1 0 39 40 2 0 40 41 1 0 5 42 1 6 15 1 1 0 27 17 1 0 34 29 1 0 40 35 1 0 27 5 1 0 41 30 1 0 17 8 1 0 26 19 1 0 28 19 1 0 1 43 1 0 2 44 1 0 3 45 1 0 3 46 1 0 4 47 1 0 4 48 1 0 6 49 1 0 8 50 1 0 9 51 1 0 9 52 1 0 10 53 1 0 10 54 1 0 12 55 1 0 12 56 1 0 13 57 1 0 13 58 1 0 14 59 1 0 14 60 1 0 15 61 1 0 15 62 1 0 16 63 1 0 16 64 1 0 18 65 1 0 18 66 1 0 20 67 1 0 20 68 1 0 21 69 1 0 21 70 1 0 22 71 1 1 23 72 1 0 23 73 1 0 24 74 1 0 24 75 1 0 25 76 1 0 25 77 1 0 27 78 1 1 32 79 1 0 33 80 1 0 36 81 1 0 37 82 1 0 38 83 1 0 39 84 1 0 41 85 1 0 42 86 1 0 M END

Standard InCHIKey	CLKZPQNKNPCQGL-NZGBLPSWSA-N
Standard InCHI	InChI=1S/C36H44N4O2/c41-35-16-7-3-1-2-4-8-19-39-21-15-29(34(24-39)23-36-17-13-25(42-36)10-9-20-40(36)33(34)35)28(22-35)31-32-27(14-18-37-31)26-11-5-6-12-30(26)38-32/h1,3,5-6,11-12,14,18,22,25,29,33,38,41H,2,4,7-10,13,15-17,19-21,23-24H2/b3-1-/t25-,29?,33+,34-,35-,36+/m0/s1
SMILES	C1=CCC[C@@]2(C=C(C3CCN(CCCC1)C[C@]13C[C@]34CC[C@H](CCCN3[C@@H]21)O4)c1c2c(ccn1)c1ccccc1[nH]2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.35	Volume:	594.68 ? Van der Waals volume.
Dense:	0.949	LogP:	3.976 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.314 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.874 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	48.0
TPSA:	64.62 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	9.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.334	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.258	Fsp³:	0.583
MCE-18:	222.632 ? 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:	0.38	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.837 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.777 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.382

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.482	MDCK Permeability:	-5.036
Pgp-inhibitor:	0.01	Pgp-substrate:	0.058
PAMPA:	0.002 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.016
50% Bioavailability (F50%):	0.044

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.992	MRP1:	0.999
Plasma Protein Binding (PPB):	75.661%	Volume Distribution (VD):	0.417
Fu:	23.994% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.008
OATP1B3 inhibitor:	0.032	BCRP inhibitor:	0.223
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.922	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.809
CYP2D6-inhibitor:	0.874	CYP2D6-substrate:	0.122
CYP3A4-inhibitor:	0.991	CYP3A4-substrate:	0.033
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.004
HLM stability:	0.739 ? 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):

9.204

Half-life (T1/2):

0.657

ADMET: Toxicity

hERG Blockers:	0.914	hERG Blockers (10um):	0.559
Human Hepatotoxicity (H-HT):	0.556	Drug-induced Liver Injury (DILI):	0.369
AMES Toxicity:	0.466	Rat Oral Acute Toxicity:	0.963
Maximum Recommended Daily Dose:	0.992	Skin Sensitization:	0.998
Carcinogencity:	0.289	Eye Corrosion:	0.0
Eye Irritation:	0.009	Respiratory Toxicity:	0.985
Drug-induced Neurotoxicity:	0.912	Ototoxicity:	0.786
Hematotoxicity:	0.101	Drug-induced Nephrotoxicity:	0.976
Genotoxicity:	0.918	RPMI-8226 Immunitoxicity:	0.345
A549 Cytotoxicity:	0.984	Hek293 Cytotoxicity:	0.967
BCF:	2.018 ? 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:	4.047 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.059 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.743 ? 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
NPO32531	sponge sp.	Species	n.a.	n.a.	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape, Manado Bay, Indonesia	2011-MAR	PMID[12828469]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15332848]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2004-Mar	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2002-May	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28452477]
NPO33515	xestospongia ashmorica	Species	Petrosiidae	Eukaryota	n.a.	Philippine	n.a.	PMID[8946747]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32531	sponge sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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

Activity Type	# Activity
Inhibition	2
ED50	1
MIC	2
IC50	13
Activity	2
EC50	2
IC90	2

Activity Type	# Activity
Individual protein	1
Cell line	4
Organism	17
Non-molecular	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT591	Individual protein	Glycogen synthase kinase-3 beta	Homo sapiens	Inhibition	=	88.4	%	PMID[23398362]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1864	Cell line	L5178Y	Mus musculus	ED50	=	1.8	ug ml-1	PMID[25682561]
NPT189	Cell line	Vero	Chlorocebus aethiops	Activity	=	4760.0	ng/ml	DrugMatrix in vitro pharmacology data
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	0.5	ug.mL-1	PMID[19702283]
NPT189	Cell line	Vero	Chlorocebus aethiops	Activity	=	4.7	ug ml-1	PMID[14695799]
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	Inhibition	=	18.5	%	PMID[16643031]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	1.3	ug.mL-1	PMID[15568794]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	1.4	ug.mL-1	PMID[22037378]
NPT86	Organism	Mycobacterium intracellulare	Mycobacterium intracellulare	IC50	=	6.25	ug.mL-1	DOI[10.1039/C5MD00178A]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	1.77	ug.mL-1	PMID[18977148]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	3.2	ug.mL-1	PMID[23002924]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	1.0	ug.mL-1	PMID[12828469]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	0.5	ug.mL-1	PMID[12828469]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC90	=	7.5	ug.mL-1	DOI[10.1016/S0960-894X(01)81072-6]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	1.8	ug.mL-1	PubChem BioAssay data set
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	1600.0	nM	PMID[19349095]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	1.5	ug.mL-1	PMID[8496701]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	IC50	=	2.0	ug.mL-1	PMID[26851505]

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 NPC471506 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	34029
0.1-0.2	15496
0.2-0.3	267
0.3-0.4	34
0.4-0.5	5
0.5-0.6	14
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8476	Intermediate Similarity	NPC81175
0.8302	Intermediate Similarity	NPC476492
0.7946	Intermediate Similarity	NPC476493
0.7944	Intermediate Similarity	NPC479688
0.7377	Intermediate Similarity	NPC471564
0.6887	Remote Similarity	NPC166492
0.6822	Remote Similarity	NPC473362
0.6577	Remote Similarity	NPC189202
0.6577	Remote Similarity	NPC479685
0.6549	Remote Similarity	NPC473310
0.6239	Remote Similarity	NPC909
0.6239	Remote Similarity	NPC475338
0.6161	Remote Similarity	NPC473757
0.5862	Remote Similarity	NPC607194
0.5826	Remote Similarity	NPC487892
0.5826	Remote Similarity	NPC6215
0.5641	Remote Similarity	NPC476451
0.5641	Remote Similarity	NPC253069
0.5641	Remote Similarity	NPC607417
0.5574	Remote Similarity	NPC41679
0.55	Remote Similarity	NPC265576
0.5492	Remote Similarity	NPC479681
0.5403	Remote Similarity	NPC473312
0.5403	Remote Similarity	NPC160752
0.5354	Remote Similarity	NPC476491
0.5276	Remote Similarity	NPC602860
0.5039	Remote Similarity	NPC475258

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471506 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5669
0.1-0.2	3442
0.2-0.3	39
0.3-0.4	0
0.4-0.5	0
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