NPASS Compound

Natural Product: NPC116377

Natural Product ID	NPC116377
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2,5-Imino-2,5,6-Trideoxy-D-Manno-Heptitol
IUPAC Name	(2R,3R,4R,5R)-2-(2-hydroxyethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol
Synonyms	6-deoxyhomoDMDP
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL407337
PubChem CID	10374978
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000218] Pyrrolidines

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 27 27 0 0 0 0 0 0 0 0999 V2000 2.1665 0.4931 -0.2185 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0149 -0.7402 -0.3312 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6123 -1.7244 0.5411 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7148 0.2074 -0.5203 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1366 1.4530 -0.4055 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5097 0.7915 -0.2475 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1571 -0.2450 0.7838 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1975 -1.3315 0.8973 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4305 -1.9952 -0.2812 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1210 -0.7452 0.3646 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3776 1.7571 0.2167 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0784 2.2571 -1.5130 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5086 1.3151 -0.8598 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2039 0.8535 0.8398 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9943 -1.0664 -1.3949 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0574 -0.4586 -0.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1866 -1.3848 1.3570 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6175 -0.1343 -1.5835 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0976 1.9736 0.5480 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7911 0.3554 -1.2094 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0901 0.2652 1.7652 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7752 -2.0849 1.6210 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1073 -0.9395 1.3936 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0787 -1.4781 -0.8204 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0365 -1.6678 -0.0978 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1911 1.3964 0.6377 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6620 2.8775 -1.4212 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 1 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 7 10 1 0 6 11 1 0 5 12 1 0 10 4 1 0 1 13 1 0 1 14 1 0 2 15 1 0 2 16 1 0 3 17 1 0 4 18 1 6 5 19 1 1 6 20 1 6 7 21 1 1 8 22 1 0 8 23 1 0 9 24 1 0 10 25 1 0 11 26 1 0 12 27 1 0 M END

Standard InCHIKey	AGFACLQFIYFFOI-DBRKOABJSA-N
Standard InCHI	InChI=1S/C7H15NO4/c9-2-1-4-6(11)7(12)5(3-10)8-4/h4-12H,1-3H2/t4-,5-,6-,7-/m1/s1
SMILES	C(CO)[C@@H]1[C@H]([C@@H]([C@@H](CO)N1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	177.1	Volume:	167.23 ? Van der Waals volume.
Dense:	1.059	LogP:	-1.895 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.548 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.515 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	5.0
TPSA:	92.95 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	5.0	Rings:	1.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.326	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.147	Fsp³:	1.0
MCE-18:	18.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.04	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.003 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.116	Promiscuous compounds:	0.279

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.783	MDCK Permeability:	-4.971
Pgp-inhibitor:	0.001	Pgp-substrate:	0.847
PAMPA:	0.972 ? 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):	0.925
20% Bioavailability (F20%):	0.424	30% Bioavailability (F30%):	0.963
50% Bioavailability (F50%):	0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.225	MRP1:	0.151
Plasma Protein Binding (PPB):	16.425%	Volume Distribution (VD):	-0.397
Fu:	88.172% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.761
OATP1B3 inhibitor:	0.929	BCRP inhibitor:	0.077
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.048	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.225
HLM stability:	0.027 ? 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):

6.13

Half-life (T1/2):

2.291

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.176
Human Hepatotoxicity (H-HT):	0.544	Drug-induced Liver Injury (DILI):	0.131
AMES Toxicity:	0.442	Rat Oral Acute Toxicity:	0.053
Maximum Recommended Daily Dose:	0.015	Skin Sensitization:	0.913
Carcinogencity:	0.253	Eye Corrosion:	0.245
Eye Irritation:	0.959	Respiratory Toxicity:	0.075
Drug-induced Neurotoxicity:	0.066	Ototoxicity:	0.781
Hematotoxicity:	0.294	Drug-induced Nephrotoxicity:	0.589
Genotoxicity:	0.021	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.016	Hek293 Cytotoxicity:	0.031
BCF:	0.1 ? 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:	1.318 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	2.38 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.747 ? 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
NPO33353	scilla sibirica	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12502331]
NPO18491	Hyacinthus orientalis	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9599261]
NPO18491	Hyacinthus orientalis	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18491	Hyacinthus orientalis	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18491	Hyacinthus orientalis	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18491	Hyacinthus orientalis	Species	Hyacinthaceae	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

Activity Type	# Activity
IC50	14
Inhibition	8

Activity Type	# Activity
Individual protein	15
Others	7

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1648	Individual protein	Oligo-1,6-glucosidase	Saccharomyces cerevisiae S288c	IC50	=	250000.0	nM	PMID[24927053]
NPT1058	Individual protein	Beta-glucosidase A	Caldicellulosiruptor saccharolyticus	IC50	=	350000.0	nM	PMID[20159656]
NPT1051	Individual protein	Lactase-glycosylceramidase	Rattus norvegicus	IC50	=	320000.0	nM	PMID[19410459]
NPT509	Individual protein	Beta-galactosidase	Bos taurus	IC50	=	88000.0	nM	PMID[15620264]
NPT462	Individual protein	Sucrase-isomaltase	Rattus norvegicus	Inhibition	<	50.0	%	PMID[18077363]
NPT462	Individual protein	Sucrase-isomaltase	Rattus norvegicus	IC50	=	11000.0	nM	PMID[18077363]
NPT5854	Individual protein	Uncharacterized protein	Sus scrofa	Inhibition	<	50.0	%	PMID[9599261]
NPT506	Individual protein	Beta-mannosidase	Rattus norvegicus	IC50	=	320000.0	nM	PMID[3934384]
NPT514	Individual protein	Glycogen debranching enzyme	Homo sapiens	IC50	=	11000.0	nM	PMID[20303767]
NPT671	Individual protein	Acidic alpha-glucosidase	Rattus norvegicus	Inhibition	<	50.0	%	PMID[23398362]
NPT496	Individual protein	Alpha-L-fucosidase 1	Bos taurus	Inhibition	<	50.0	%	PMID[17279797]
NPT671	Individual protein	Acidic alpha-glucosidase	Rattus norvegicus	IC50	=	2500.0	nM	PMID[20594858]
NPT671	Individual protein	Acidic alpha-glucosidase	Rattus norvegicus	IC50	=	7200.0	nM	PMID[17064068]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Inhibition	<	50.0	%	PMID[17993275]
NPT2	Others	Unspecified	n.a.	IC50	=	94000.0	nM	PMID[15620264]
NPT2	Others	Unspecified	n.a.	IC50	=	2200.0	nM	PMID[20594858]
NPT2	Others	Unspecified	n.a.	IC50	=	380000.0	nM	PMID[12608862]
NPT2	Others	Unspecified	n.a.	IC50	=	60000.0	nM	PMID[17691763]

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 NPC116377 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	46002
0.1-0.2	3700
0.2-0.3	109
0.3-0.4	22
0.4-0.5	19
0.5-0.6	3
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC69798
0.6538	Remote Similarity	NPC473710
0.5909	Remote Similarity	NPC62507
0.5909	Remote Similarity	NPC602743
0.5172	Remote Similarity	NPC268922

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC116377 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8376
0.1-0.2	743
0.2-0.3	26
0.3-0.4	5
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