NPASS Compound

Structure

Physi-Chem Properties

Molecular Weight:	184.08
Volume:	172.903
LogP:	-0.994
LogD:	-1.323
LogS:	-0.768
# Rotatable Bonds:	0
TPSA:	69.64
# H-Bond Aceptor:	5
# H-Bond Donor:	2
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.479
Synthetic Accessibility Score:	3.517
Fsp3:	0.75
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.442
MDCK Permeability:	0.00012724011321552098
Pgp-inhibitor:	0.0
Pgp-substrate:	0.611
Human Intestinal Absorption (HIA):	0.118
20% Bioavailability (F20%):	0.058
30% Bioavailability (F30%):	0.053

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.186
Plasma Protein Binding (PPB):	5.7879743576049805%
Volume Distribution (VD):	0.636
Pgp-substrate:	88.03556823730469%

ADMET: Metabolism

CYP1A2-inhibitor:	0.008
CYP1A2-substrate:	0.075
CYP2C19-inhibitor:	0.035
CYP2C19-substrate:	0.282
CYP2C9-inhibitor:	0.01
CYP2C9-substrate:	0.164
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.158
CYP3A4-inhibitor:	0.007
CYP3A4-substrate:	0.11

ADMET: Excretion

Clearance (CL):	2.72
Half-life (T1/2):	0.582

ADMET: Toxicity

hERG Blockers:	0.01
Human Hepatotoxicity (H-HT):	0.904
Drug-inuced Liver Injury (DILI):	0.52
AMES Toxicity:	0.01
Rat Oral Acute Toxicity:	0.037
Maximum Recommended Daily Dose:	0.852
Skin Sensitization:	0.15
Carcinogencity:	0.023
Eye Corrosion:	0.003
Eye Irritation:	0.043
Respiratory Toxicity:	0.163

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC126186

Natural Product ID:	NPC126186
*Common Name:**	Cyclo-(L-Alanyl-Trans-4-Hydroxy-L-Prolyl)
IUPAC Name:	(3S,7R,8aS)-7-hydroxy-3-methyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:
Standard InCHIKey:	JBVUOARNEYAAOS-JKUQZMGJSA-N
Standard InCHI:	InChI=1S/C8H12N2O3/c1-4-8(13)10-3-5(11)2-6(10)7(12)9-4/h4-6,11H,2-3H2,1H3,(H,9,12)/t4-,5+,6-/m0/s1
SMILES:	C[C@H]1C(=O)N2C[C@@H](C[C@H]2C(=N1)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL456087
PubChem CID:	21580253
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:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	red sea	n.a.	PMID[12762806]
NPO20897.1	Suberites domuncula	Under-species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[15270577]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17616609]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17929896]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[18027906]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19113967]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19159274]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19256529]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu	2003	PMID[20303767]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21667925]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21954885]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22106303]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	stem bark of Melia azedarach	n.a.	n.a.	PMID[22409377]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22469701]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23557488]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23563483]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	collected by hand at a depth of 10 m off the shore of Iriomote Island, Okinawa Prefecture, Japan	2009-JUN	PMID[23855338]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[24948562]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[27015002]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7622436]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	New Guinea	n.a.	PMID[8158156]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10538	Aspergillus fumigatus	Species	Aspergillaceae	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	NP ID	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
Others	5

Activity Type	# Activity
Cell Line	4
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1182	Cell Line	J774.A1	Mus musculus	FC	=	1.65	n.a.	PMID[508862]
NPT1182	Cell Line	J774.A1	Mus musculus	FC	=	4.49	n.a.	PMID[508862]
NPT1182	Cell Line	J774.A1	Mus musculus	FC	=	3.09	n.a.	PMID[508862]
NPT1182	Cell Line	J774.A1	Mus musculus	FC	=	1.12	n.a.	PMID[508862]
NPT176	Organism	Artemia salina	Artemia salina	LC50	=	66.1	ug.mL-1	PMID[508863]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC126186 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	280
0.1-0.2	20657
0.2-0.3	17981
0.3-0.4	2574
0.4-0.5	857
0.5-0.6	255
0.6-0.7	60
0.7-0.8	17
0.8-0.85	10
0.85-0.9	2
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9429	High Similarity	NPC470782
0.913	High Similarity	NPC470781
0.9054	High Similarity	NPC470783
0.8955	High Similarity	NPC128005
0.8955	High Similarity	NPC84182
0.8507	High Similarity	NPC243964
0.8333	Intermediate Similarity	NPC214532
0.8333	Intermediate Similarity	NPC76297
0.8333	Intermediate Similarity	NPC196007
0.8289	Intermediate Similarity	NPC312315
0.8108	Intermediate Similarity	NPC161774
0.8108	Intermediate Similarity	NPC266888
0.8108	Intermediate Similarity	NPC209156
0.8108	Intermediate Similarity	NPC256312
0.7595	Intermediate Similarity	NPC31756
0.75	Intermediate Similarity	NPC476117
0.75	Intermediate Similarity	NPC476156
0.75	Intermediate Similarity	NPC476243
0.75	Intermediate Similarity	NPC476137
0.7407	Intermediate Similarity	NPC476302
0.7407	Intermediate Similarity	NPC475542
0.7326	Intermediate Similarity	NPC275715
0.7125	Intermediate Similarity	NPC329077
0.7051	Intermediate Similarity	NPC29326
0.7045	Intermediate Similarity	NPC475801
0.7045	Intermediate Similarity	NPC474593
0.6977	Remote Similarity	NPC477539
0.6966	Remote Similarity	NPC474576
0.6914	Remote Similarity	NPC59867
0.6889	Remote Similarity	NPC173763
0.6889	Remote Similarity	NPC471098
0.6889	Remote Similarity	NPC62263
0.68	Remote Similarity	NPC160661
0.6774	Remote Similarity	NPC473597
0.6667	Remote Similarity	NPC322274
0.6632	Remote Similarity	NPC475440
0.6627	Remote Similarity	NPC325902
0.6531	Remote Similarity	NPC476877
0.6494	Remote Similarity	NPC287693
0.6479	Remote Similarity	NPC275727
0.6465	Remote Similarity	NPC128303
0.6458	Remote Similarity	NPC475758
0.6421	Remote Similarity	NPC134504
0.6421	Remote Similarity	NPC47076
0.6413	Remote Similarity	NPC477538
0.64	Remote Similarity	NPC476876
0.64	Remote Similarity	NPC241394
0.6392	Remote Similarity	NPC475791
0.6392	Remote Similarity	NPC13175
0.6265	Remote Similarity	NPC327272
0.6263	Remote Similarity	NPC475149
0.6263	Remote Similarity	NPC471097
0.6238	Remote Similarity	NPC475637
0.6154	Remote Similarity	NPC163352
0.6154	Remote Similarity	NPC210456
0.6154	Remote Similarity	NPC233034
0.6145	Remote Similarity	NPC320221
0.6136	Remote Similarity	NPC319753
0.6111	Remote Similarity	NPC325723
0.6095	Remote Similarity	NPC476875
0.6044	Remote Similarity	NPC43246
0.6044	Remote Similarity	NPC89051
0.6026	Remote Similarity	NPC57420
0.6	Remote Similarity	NPC78312
0.6	Remote Similarity	NPC59221
0.6	Remote Similarity	NPC135539
0.6	Remote Similarity	NPC221764
0.6	Remote Similarity	NPC196359
0.5981	Remote Similarity	NPC63191
0.5981	Remote Similarity	NPC471202
0.598	Remote Similarity	NPC323720
0.596	Remote Similarity	NPC220234
0.5955	Remote Similarity	NPC184473
0.5952	Remote Similarity	NPC315806
0.5949	Remote Similarity	NPC472609
0.5926	Remote Similarity	NPC74555
0.5926	Remote Similarity	NPC266242
0.5926	Remote Similarity	NPC254617
0.5926	Remote Similarity	NPC34291
0.5926	Remote Similarity	NPC306763
0.5926	Remote Similarity	NPC126664
0.589	Remote Similarity	NPC178263
0.589	Remote Similarity	NPC272396
0.589	Remote Similarity	NPC277072
0.5875	Remote Similarity	NPC294883
0.5875	Remote Similarity	NPC12514
0.5872	Remote Similarity	NPC296043
0.5867	Remote Similarity	NPC65832
0.5867	Remote Similarity	NPC10262
0.5867	Remote Similarity	NPC311668
0.5854	Remote Similarity	NPC475127
0.5854	Remote Similarity	NPC473419
0.5854	Remote Similarity	NPC475715
0.5851	Remote Similarity	NPC315063
0.5824	Remote Similarity	NPC112842
0.5824	Remote Similarity	NPC71339
0.5818	Remote Similarity	NPC329216
0.5802	Remote Similarity	NPC184150
0.5802	Remote Similarity	NPC141156
0.5784	Remote Similarity	NPC5864
0.5784	Remote Similarity	NPC124554
0.5784	Remote Similarity	NPC301148
0.5783	Remote Similarity	NPC163538
0.5783	Remote Similarity	NPC115800
0.5778	Remote Similarity	NPC84128
0.5778	Remote Similarity	NPC53858
0.5769	Remote Similarity	NPC314510
0.5769	Remote Similarity	NPC30126
0.5769	Remote Similarity	NPC474014
0.5769	Remote Similarity	NPC57846
0.5753	Remote Similarity	NPC137327
0.5752	Remote Similarity	NPC315188
0.5732	Remote Similarity	NPC474469
0.5732	Remote Similarity	NPC171850
0.5728	Remote Similarity	NPC198344
0.5714	Remote Similarity	NPC106780
0.5714	Remote Similarity	NPC469899
0.5714	Remote Similarity	NPC473599
0.5699	Remote Similarity	NPC469363
0.5694	Remote Similarity	NPC224624
0.569	Remote Similarity	NPC474082
0.569	Remote Similarity	NPC175726
0.5684	Remote Similarity	NPC109188
0.5684	Remote Similarity	NPC322966
0.5684	Remote Similarity	NPC171116
0.5673	Remote Similarity	NPC124549
0.567	Remote Similarity	NPC315237
0.566	Remote Similarity	NPC67009
0.566	Remote Similarity	NPC207820
0.5657	Remote Similarity	NPC117829
0.5652	Remote Similarity	NPC472351
0.5644	Remote Similarity	NPC475188
0.5614	Remote Similarity	NPC160688
0.5612	Remote Similarity	NPC17892
0.5612	Remote Similarity	NPC36985
0.5604	Remote Similarity	NPC246005
0.5604	Remote Similarity	NPC6902

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC126186 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	96
0.1-0.2	2548
0.2-0.3	4958
0.3-0.4	1157
0.4-0.5	300
0.5-0.6	69
0.6-0.7	18
0.7-0.8	4
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
0.7412	Intermediate Similarity	NPD3177	Phase 3
0.7317	Intermediate Similarity	NPD2683	Discontinued
0.7176	Intermediate Similarity	NPD3723	Clinical (unspecified phase)
0.6974	Remote Similarity	NPD322	Phase 1
0.6966	Remote Similarity	NPD4261	Phase 1
0.6857	Remote Similarity	NPD1456	Approved
0.6786	Remote Similarity	NPD7762	Phase 2
0.6786	Remote Similarity	NPD7763	Phase 2
0.6778	Remote Similarity	NPD4780	Clinical (unspecified phase)
0.6761	Remote Similarity	NPD9425	Approved
0.6667	Remote Similarity	NPD7841	Clinical (unspecified phase)
0.6575	Remote Similarity	NPD8951	Approved
0.6526	Remote Similarity	NPD8038	Phase 2
0.6512	Remote Similarity	NPD1125	Discovery
0.6404	Remote Similarity	NPD7760	Phase 2
0.6404	Remote Similarity	NPD7759	Phase 2
0.6364	Remote Similarity	NPD9577	Approved
0.6292	Remote Similarity	NPD9401	Discovery
0.625	Remote Similarity	NPD620	Approved
0.62	Remote Similarity	NPD6122	Discontinued
0.6154	Remote Similarity	NPD9440	Discontinued
0.6081	Remote Similarity	NPD581	Approved
0.6081	Remote Similarity	NPD843	Clinical (unspecified phase)
0.6081	Remote Similarity	NPD583	Approved
0.6081	Remote Similarity	NPD584	Approved
0.6044	Remote Similarity	NPD9581	Clinical (unspecified phase)
0.6044	Remote Similarity	NPD9580	Clinical (unspecified phase)
0.6022	Remote Similarity	NPD755	Phase 3
0.6	Remote Similarity	NPD8868	Approved
0.5976	Remote Similarity	NPD9649	Approved
0.5976	Remote Similarity	NPD2220	Clinical (unspecified phase)
0.5952	Remote Similarity	NPD9653	Clinical (unspecified phase)
0.593	Remote Similarity	NPD9199	Approved
0.5926	Remote Similarity	NPD9443	Clinical (unspecified phase)
0.5895	Remote Similarity	NPD251	Approved
0.5857	Remote Similarity	NPD362	Phase 1
0.5843	Remote Similarity	NPD9558	Phase 3
0.5824	Remote Similarity	NPD280	Approved
0.5789	Remote Similarity	NPD9565	Discontinued
0.5783	Remote Similarity	NPD1439	Clinical (unspecified phase)
0.5775	Remote Similarity	NPD8950	Approved
0.5769	Remote Similarity	NPD1385	Discontinued
0.5732	Remote Similarity	NPD9444	Discontinued
0.5714	Remote Similarity	NPD883	Phase 2
0.5714	Remote Similarity	NPD882	Phase 2
0.5699	Remote Similarity	NPD240	Phase 3
0.5699	Remote Similarity	NPD5791	Phase 2
0.5698	Remote Similarity	NPD9198	Approved
0.5684	Remote Similarity	NPD1331	Approved
0.567	Remote Similarity	NPD1686	Approved
0.567	Remote Similarity	NPD279	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD9556	Approved
0.5652	Remote Similarity	NPD3733	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD238	Clinical (unspecified phase)
0.5652	Remote Similarity	NPD239	Phase 2
0.5647	Remote Similarity	NPD265	Phase 3
0.5647	Remote Similarity	NPD266	Phase 3
0.5632	Remote Similarity	NPD9407	Approved
0.5618	Remote Similarity	NPD4815	Discontinued
0.5604	Remote Similarity	NPD9560	Approved
0.5604	Remote Similarity	NPD9561	Approved

Bioactivity similarity: Similar Natural Products in NPASS

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