NPASS Compound

Natural Product: NPC479753

Natural Product ID	NPC479753
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PRQZJBRLTLSRGU-YWQVJIEVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	18608376
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 70 71 0 0 0 0 0 0 0 0999 V2000 -5.2231 -3.9736 -0.4941 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4843 -2.8791 0.2442 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8841 -1.8856 -0.6921 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9124 -2.5561 -1.6064 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2888 -0.6938 0.0228 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6988 0.2785 -0.9337 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4691 0.5628 -0.8653 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7340 1.4617 -1.6872 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9994 2.9235 -1.3225 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6322 3.2279 0.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5711 3.0772 1.0579 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2833 3.3495 2.3855 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0374 3.7810 2.7357 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9205 3.9405 1.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6208 3.6630 0.4225 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7479 1.1546 -1.5861 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1325 0.2319 -0.8405 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3664 -0.3315 -0.4943 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3070 -0.6646 -1.6169 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5689 -1.2544 -1.1154 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6285 -2.6197 -0.9456 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7748 -3.2201 -0.4870 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8988 -2.5043 -0.1802 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8541 -1.1356 -0.3453 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6994 -0.5274 -0.8076 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0510 -3.1510 0.2855 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1514 0.6021 0.8466 P 0 0 0 0 0 0 0 0 0 0 0 0 2.1397 0.9333 1.9317 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3740 -0.2929 1.6004 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7924 2.0725 0.3273 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5530 1.9776 -2.3759 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4650 0.8941 -1.9144 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3138 0.0080 0.7691 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.2014 0.3702 1.9864 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3696 1.0870 2.5915 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0462 0.0941 2.6681 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1441 -4.9175 0.0499 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8265 -4.1024 -1.5242 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2831 -3.6410 -0.6091 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2046 -2.4340 0.9602 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6939 -3.3940 0.8590 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7162 -1.4869 -1.3306 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8479 -3.6280 -1.3361 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2133 -2.5121 -2.6744 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9004 -2.1347 -1.4378 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5275 -1.0677 0.7052 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9652 1.3731 -2.7687 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0733 3.0964 -1.5422 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4409 3.5818 -2.0232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5623 2.7389 0.8151 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0269 3.2277 3.1562 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1843 3.9957 3.7940 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8940 4.2790 2.0451 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4004 3.7995 -0.3233 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1271 -1.3455 -0.0113 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5190 0.1439 -2.3161 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8098 -1.4640 -2.2440 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7578 -3.2511 -1.1749 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8003 -4.2996 -0.3602 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7499 -0.5819 -0.0991 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6865 0.5528 -0.9328 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4694 -3.9318 -0.1943 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0240 -0.7869 2.4021 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7525 2.7383 1.0593 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4677 2.2339 -2.0379 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9929 1.1510 -2.7689 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2081 0.3818 2.7766 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0944 1.5386 3.5688 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7414 1.8842 1.9245 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 0.2607 2.2050 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 3 5 1 0 5 6 1 0 6 7 2 3 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 8 16 1 0 16 17 2 3 17 18 1 0 18 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 23 26 1 0 18 27 1 0 27 28 2 0 27 29 1 0 27 30 1 0 16 31 1 0 6 32 1 0 5 33 1 0 33 34 2 3 34 35 1 0 34 36 1 0 15 10 1 0 25 20 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 2 41 1 0 3 42 1 6 4 43 1 0 4 44 1 0 4 45 1 0 5 46 1 1 8 47 1 6 9 48 1 0 9 49 1 0 11 50 1 0 12 51 1 0 13 52 1 0 14 53 1 0 15 54 1 0 18 55 1 1 19 56 1 0 19 57 1 0 21 58 1 0 22 59 1 0 24 60 1 0 25 61 1 0 26 62 1 0 29 63 1 0 30 64 1 0 31 65 1 0 32 66 1 0 35 67 1 0 35 68 1 0 35 69 1 0 36 70 1 0 M END

Standard InCHIKey	PRQZJBRLTLSRGU-YWQVJIEVSA-N
Standard InCHI	InChI=1S/C25H34N3O7P/c1-4-16(2)23(26-17(3)29)25(32)27-21(14-18-8-6-5-7-9-18)24(31)28-22(36(33,34)35)15-19-10-12-20(30)13-11-19/h5-13,16,21-23,30H,4,14-15H2,1-3H3,(H,26,29)(H,27,32)(H,28,31)(H2,33,34,35)/t16-,21-,22+,23-/m0/s1
SMILES	CC[C@H](C)[C@@H](C(=N[C@@H](Cc1ccccc1)C(=N[C@@H](Cc1ccc(cc1)O)P(=O)(O)O)O)O)N=C(C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	519.21	Volume:	514.464 ? Van der Waals volume.
Dense:	1.009	LogP:	1.301 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.87 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.766 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	16.0
TPSA:	175.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	2.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.137	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.485	Fsp³:	0.4
MCE-18:	38.0 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.597	Fluc inhibitor:	0.311 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.42 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.016	Promiscuous compounds:	0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.802	MDCK Permeability:	-4.972
Pgp-inhibitor:	0.003	Pgp-substrate:	0.909
PAMPA:	0.996 ? 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):	0.039
20% Bioavailability (F20%):	0.994	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.237
Plasma Protein Binding (PPB):	87.025%	Volume Distribution (VD):	-0.486
Fu:	8.346% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.031
BSEP inhibitor:	0.866

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.055	CYP2C19-substrate:	0.625
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
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):

1.215

Half-life (T1/2):

1.766

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.001
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.021	Rat Oral Acute Toxicity:	0.117
Maximum Recommended Daily Dose:	0.998	Skin Sensitization:	1.0
Carcinogencity:	0.006	Eye Corrosion:	0.0
Eye Irritation:	0.228	Respiratory Toxicity:	0.994
Drug-induced Neurotoxicity:	0.065	Ototoxicity:	0.987
Hematotoxicity:	0.013	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.0
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.228
BCF:	0.335 ? 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:	3.032 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.346 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.505 ? 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
NPO40775	Actinomycetes sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[24900839]
NPO40775	Actinomycetes 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
Ratio Ki	1
Ki	2
IC50	3

Activity Type	# Activity
Individual protein	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Ratio Ki	=	15.0	n.a.	PMID[24900839]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Ki	=	12.0	nM	PMID[24900839]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Ki	=	170.0	nM	PMID[24900839]
NPT276	Individual protein	Angiotensin-converting enzyme	Oryctolagus cuniculus	IC50	=	35.0	nM	PMID[24900839]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	IC50	=	7.0	nM	PMID[24900839]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	IC50	=	88.0	nM	PMID[24900839]

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 NPC479753 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	15249
0.1-0.2	30114
0.2-0.3	4097
0.3-0.4	302
0.4-0.5	67
0.5-0.6	13
0.6-0.7	13
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9184	High Similarity	NPC479749
0.7455	Intermediate Similarity	NPC479752
0.6939	Remote Similarity	NPC82963
0.6833	Remote Similarity	NPC479750
0.68	Remote Similarity	NPC25565
0.68	Remote Similarity	NPC475439
0.6724	Remote Similarity	NPC486124
0.6349	Remote Similarity	NPC479754
0.625	Remote Similarity	NPC88267
0.6182	Remote Similarity	NPC118202
0.6167	Remote Similarity	NPC479751
0.6122	Remote Similarity	NPC38458
0.6122	Remote Similarity	NPC311737
0.6034	Remote Similarity	NPC224610
0.6034	Remote Similarity	NPC113326
0.5645	Remote Similarity	NPC254088
0.5577	Remote Similarity	NPC303045
0.5455	Remote Similarity	NPC483337
0.5375	Remote Similarity	NPC489825
0.5375	Remote Similarity	NPC489826
0.5306	Remote Similarity	NPC311242
0.5278	Remote Similarity	NPC242482
0.5273	Remote Similarity	NPC161972
0.5205	Remote Similarity	NPC224315
0.5172	Remote Similarity	NPC194390
0.5119	Remote Similarity	NPC302597
0.5094	Remote Similarity	NPC621
0.5068	Remote Similarity	NPC6570

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479753 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	1903
0.1-0.2	6356
0.2-0.3	836
0.3-0.4	47
0.4-0.5	8
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