NPASS Compound

Natural Product: NPC313640

Natural Product ID	NPC313640
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Phosphoramidon
IUPAC Name	(2S)-2-[[(2S)-2-[[hydroxy-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid
Synonyms	Phosphoramidon; Phosphramidon; Phosporamidon
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479579
PubChem CID	445114
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004830] Dipeptides

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 71 73 0 0 0 0 0 0 0 0999 V2000 -5.4569 -1.8887 0.4897 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9778 -0.5489 -0.0494 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9971 0.0533 0.8493 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5569 1.2130 1.6611 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4392 2.0083 1.0214 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3989 0.9461 0.6363 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9319 0.2561 -0.4160 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1371 1.4412 0.4884 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0648 0.8630 1.6861 P 0 0 0 0 0 0 0 0 0 0 0 0 -2.5257 -0.4432 2.2263 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4817 0.8730 1.0559 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.1221 -0.3861 0.3291 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0142 -0.5013 -0.8349 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9559 -1.6391 -1.7745 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3073 -1.8440 -2.5487 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1020 -1.4490 -2.7941 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2930 -0.1959 0.0109 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7374 1.0212 0.0013 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2566 -1.1944 -0.2788 N 0 0 0 0 0 0 0 0 0 0 0 0 3.6298 -0.7427 -0.5439 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5166 -1.1618 0.6271 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8864 -0.6973 0.3576 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9704 -1.4304 -0.0328 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0234 -0.6012 -0.1533 N 0 0 0 0 0 0 0 0 0 0 0 0 7.6171 0.6502 0.1569 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3293 1.8459 0.1807 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6541 2.9977 0.5399 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3154 2.9869 0.8689 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6159 1.7999 0.8434 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2776 0.6468 0.4869 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1304 -1.4509 -1.7334 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4768 -2.3378 -2.3036 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4026 -1.0822 -2.2169 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1484 2.0151 2.9468 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9057 2.8927 1.9262 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6244 2.0290 2.0020 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4128 -0.9610 1.7446 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0397 -1.8004 1.5055 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2745 -2.6542 0.4645 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6384 -2.1879 -0.1952 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5147 -0.8299 -1.0050 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9382 0.3303 0.3046 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1236 0.8476 2.6379 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8451 2.5049 0.1266 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3593 0.2583 1.5337 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2223 1.6856 0.4895 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2602 -1.1897 1.0577 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9173 0.4318 -1.5126 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1111 -0.3910 -0.5356 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1427 -2.6300 -1.2611 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0365 -2.0521 -3.6435 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8389 -2.7756 -2.2552 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9235 -0.9411 -2.6103 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7195 -0.5567 -2.5297 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6855 -2.3709 -2.8870 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6494 -1.2128 -3.7722 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9791 -2.1763 -0.2795 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6755 0.3453 -0.6098 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5023 -2.2567 0.6765 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1497 -0.7188 1.5782 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9830 -2.5012 -0.2154 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9800 -0.8756 -0.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3590 1.8171 -0.0782 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2209 3.9147 0.5534 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8489 3.9331 1.1417 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5744 1.7531 1.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5576 -1.3125 -3.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4788 1.8143 3.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7439 3.7722 1.4719 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9155 2.6356 1.2685 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2363 -0.5935 2.1696 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 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 14 16 1 0 12 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 20 31 1 0 31 32 2 0 31 33 1 0 9 34 1 0 5 35 1 0 4 36 1 0 3 37 1 0 7 2 1 0 30 22 1 0 30 25 1 0 1 38 1 0 1 39 1 0 1 40 1 0 2 41 1 0 3 42 1 0 4 43 1 0 5 44 1 0 6 45 1 0 11 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 15 53 1 0 16 54 1 0 16 55 1 0 16 56 1 0 19 57 1 0 20 58 1 0 21 59 1 0 21 60 1 0 23 61 1 0 24 62 1 0 26 63 1 0 27 64 1 0 28 65 1 0 29 66 1 0 33 67 1 0 34 68 1 0 35 69 1 0 36 70 1 0 37 71 1 0 M END

Standard InCHIKey	ZPHBZEQOLSRPAK-XLCYBJAPSA-N
Standard InCHI	InChI=1S/C23H34N3O10P/c1-11(2)8-16(26-37(33,34)36-23-20(29)19(28)18(27)12(3)35-23)21(30)25-17(22(31)32)9-13-10-24-15-7-5-4-6-14(13)15/h4-7,10-12,16-20,23-24,27-29H,8-9H2,1-3H3,(H,25,30)(H,31,32)(H2,26,33,34)/t12-,16-,17-,18-,19+,20+,23-/m0/s1
SMILES	CC1C(C(C(C(O1)OP(=O)(NC(CC(C)C)C(=O)NC(CC2=CNC3=CC=CC=C32)C(=O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	543.2	Volume:	505.596 ? Van der Waals volume.
Dense:	1.074	LogP:	-0.258 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.083 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.88 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	19.0
TPSA:	210.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	3.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.18	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.359	Fsp³:	0.565
MCE-18:	81.944 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.035	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.044 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.543 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.022	Promiscuous compounds:	0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.117	MDCK Permeability:	-5.193
Pgp-inhibitor:	0.0	Pgp-substrate:	0.0
PAMPA:	0.999 ? 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):	0.268
20% Bioavailability (F20%):	0.406	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.153
Plasma Protein Binding (PPB):	66.939%	Volume Distribution (VD):	-0.662
Fu:	32.311% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.977
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.0
BSEP inhibitor:	0.72

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.037	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	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:	0.0
HLM stability:	0.029 ? 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):

1.682

Half-life (T1/2):

2.004

ADMET: Toxicity

hERG Blockers:	0.003	hERG Blockers (10um):	0.017
Human Hepatotoxicity (H-HT):	0.695	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.154	Rat Oral Acute Toxicity:	0.279
Maximum Recommended Daily Dose:	0.567	Skin Sensitization:	0.006
Carcinogencity:	0.403	Eye Corrosion:	0.0
Eye Irritation:	0.128	Respiratory Toxicity:	0.145
Drug-induced Neurotoxicity:	0.703	Ototoxicity:	0.926
Hematotoxicity:	0.125	Drug-induced Nephrotoxicity:	0.963
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.01
A549 Cytotoxicity:	0.003	Hek293 Cytotoxicity:	0.052
BCF:	0.255 ? 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:	3.034 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.825 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.766 ? 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
NPO25111	Streptomyces tanashiensis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	DOI[10.1016/S0040-4039(01)84249-0]
NPO25111	Streptomyces tanashiensis	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25111	Streptomyces tanashiensis	Species	Streptomycetaceae	Bacteria	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

Activity Type	# Activity
IC50	34
Inhibition	5
Ki	4
Log Kd	1
Ratio	1

Activity Type	# Activity
Individual protein	35
Organism	2
Single protein	2
Others	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	27.0	nM	PMID[8120868]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	30.0	nM	PMID[10669576]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	4.2	nM	DOI[10.1016/0960-894X(96)00211-9]
NPT2977	Individual protein	Thermolysin	Bacillus thermoproteolyticus	Ki	=	28.0	nM	PMID[1588550]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	26.0	nM	PMID[8544178]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	200.0	nM	PMID[12852763]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	0.6	nM	PMID[2585440]
NPT2977	Individual protein	Thermolysin	Bacillus thermoproteolyticus	IC50	=	33.0	nM	PMID[7783143]
NPT2977	Individual protein	Thermolysin	Bacillus thermoproteolyticus	Log Kd	=	-7.56	n.a.	PMID[12061879]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	Ki	=	4.0	nM	PMID[2993614]
NPT1554	Individual protein	Neprilysin	Rattus norvegicus	IC50	=	34.0	nM	PMID[32337993]
NPT5879	Individual protein	Neprilysin	Homo sapiens	IC50	=	30.0	nM	PMID[19899765]
NPT5879	Individual protein	Neprilysin	Homo sapiens	IC50	=	100.0	nM	PMID[12852763]
NPT5881	Individual protein	Neprilysin	Oryctolagus cuniculus	IC50	=	0.4	nM	PMID[2585440]
NPT5881	Individual protein	Neprilysin	Oryctolagus cuniculus	IC50	=	2.0	nM	PMID[7783143]
NPT5881	Individual protein	Neprilysin	Oryctolagus cuniculus	IC50	=	6.0	nM	PMID[7783143]
NPT5879	Individual protein	Neprilysin	Homo sapiens	IC50	=	2.0	nM	PMID[21937235]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	2.55	%	DOI[10.6019/CHEMBL4495564]
NPT25696	Single protein	Pseudolysin	Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228)	Ki	=	57.0	nM	PMID[26804741]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	Inhibition	=	47.0	%	PMID[10669576]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	1200.0	nM	PMID[19899765]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	500.0	nM	DOI[10.1016/0960-894X(96)00297-1]
NPT5880	Individual protein	Endothelin-converting enzyme 1	Bos taurus	IC50	=	3100.0	nM	DOI[10.1016/S0960-894X(01)80341-3]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	2000.0	nM	PMID[8421284]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	800.0	nM	PMID[15658862]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	100.0	nM	DOI[10.1016/0960-894X(96)00211-9]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	4000.0	nM	DOI[10.1016/S0960-894X(01)80994-X]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	0.8	nM	PMID[7783143]
NPT5878	Individual protein	Endothelin-converting enzyme 1	Homo sapiens	IC50	=	17.0	nM	PMID[19596577]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.11	%	DOI[10.6019/CHEMBL4495565]
NPT2	Others	Unspecified	n.a.	Ratio	=	1.4	n.a.	DOI[10.1016/S0960-894X(01)80341-3]
NPT2	Others	Unspecified	n.a.	IC50	=	13800.0	nM	PMID[17933532]
NPT2	Others	Unspecified	n.a.	Ki	=	6980.0	nM	PMID[17933532]
NPT2	Others	Unspecified	n.a.	IC50	=	600.0	nM	PMID[15921434]
NPT2	Others	Unspecified	n.a.	IC50	=	2100.0	nM	PMID[18588282]
NPT2	Others	Unspecified	n.a.	IC50	=	7630.0	nM	PMID[20053563]

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 NPC313640 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	15670
0.1-0.2	31916
0.2-0.3	2003
0.3-0.4	251
0.4-0.5	16
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	Natural Product ID
		NPC

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC313640 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3387
0.1-0.2	5576
0.2-0.3	159
0.3-0.4	28
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