NPASS Compound

Structure

NPC9436 OpenBabel07101718312D 27 28 0 0 1 0 0 0 0 0999 V2000 -8.6603 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8660 -2.5000 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.0000 1.7321 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 3 13 1 0 0 0 0 4 14 1 0 0 0 0 6 12 1 0 0 0 0 7 8 2 0 0 0 0 7 13 1 0 0 0 0 8 15 1 0 0 0 0 9 12 1 0 0 0 0 9 13 2 0 0 0 0 10 15 2 0 0 0 0 10 16 1 0 0 0 0 11 17 2 0 0 0 0 11 23 1 0 0 0 0 12 2 1 1 0 0 0 14 24 2 0 0 0 0 14 27 1 0 0 0 0 15 23 1 0 0 0 0 16 17 1 0 0 0 0 16 18 2 0 0 0 0 17 19 1 0 0 0 0 18 20 1 0 0 0 0 18 22 1 0 0 0 0 19 21 1 0 0 0 0 19 25 2 0 0 0 0 20 21 1 0 0 0 0 20 26 2 0 0 0 0 21 5 1 6 0 0 0 21 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	389.14
Volume:	394.936
LogP:	3.125
LogD:	2.306
LogS:	-3.141
# Rotatable Bonds:	6
TPSA:	73.33
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	2
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.325
Synthetic Accessibility Score:	4.396
Fsp3:	0.429
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.663
MDCK Permeability:	2.6002278900705278e-05
Pgp-inhibitor:	0.591
Pgp-substrate:	0.009
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.693
Plasma Protein Binding (PPB):	93.0971908569336%
Volume Distribution (VD):	2.284
Pgp-substrate:	8.499927520751953%

ADMET: Metabolism

CYP1A2-inhibitor:	0.069
CYP1A2-substrate:	0.508
CYP2C19-inhibitor:	0.639
CYP2C19-substrate:	0.893
CYP2C9-inhibitor:	0.515
CYP2C9-substrate:	0.267
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.358
CYP3A4-inhibitor:	0.674
CYP3A4-substrate:	0.746

ADMET: Excretion

Clearance (CL):	1.351
Half-life (T1/2):	0.786

ADMET: Toxicity

hERG Blockers:	0.031
Human Hepatotoxicity (H-HT):	0.244
Drug-inuced Liver Injury (DILI):	0.931
AMES Toxicity:	0.023
Rat Oral Acute Toxicity:	0.185
Maximum Recommended Daily Dose:	0.933
Skin Sensitization:	0.45
Carcinogencity:	0.278
Eye Corrosion:	0.012
Eye Irritation:	0.022
Respiratory Toxicity:	0.814

Download Data

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

Natural Product: NPC9436

Natural Product ID:	NPC9436
*Common Name:**	Sclerotioramine
IUPAC Name:	[(7R)-5-chloro-3-[(1E,3E,5S)-3,5-dimethylhepta-1,3-dienyl]-7-methyl-6,8-dioxo-2H-isoquinolin-7-yl] acetate
Synonyms:	Sclerotioramine
Standard InCHIKey:	DOUKEKLEUAGITQ-UPWXJBBJSA-N
Standard InCHI:	InChI=1S/C21H24ClNO4/c1-6-12(2)9-13(3)7-8-15-10-16-17(11-23-15)19(25)21(5,27-14(4)24)20(26)18(16)22/h7-12,23H,6H2,1-5H3/b8-7+,13-9+/t12-,21+/m0/s1
SMILES:	CC[C@@H](/C=C(/C=C/c1[nH]cc2c(=C(Cl)C(=O)[C@](C2=O)(C)OC(=O)C)c1)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1097682
PubChem CID:	46888543
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0003477] Azaphilones

*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
NPO26654	Penicillium citreonigrum	Species	Aspergillaceae	Eukaryota	n.a.	atlantic-forest-soil	n.a.	PMID[20450206]
NPO26654	Penicillium citreonigrum	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
Organism	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	IZ	=	8.0	mm	PMID[458662]
NPT20	Organism	Candida albicans	Candida albicans	IZ	=	8.0	mm	PMID[458662]
NPT188	Organism	Candida parapsilosis	Candida parapsilosis	IZ	=	7.0	mm	PMID[458662]
NPT186	Organism	Candida tropicalis	Candida tropicalis	IZ	=	8.0	mm	PMID[458662]
NPT187	Organism	Issatchenkia orientalis	Pichia kudriavzevii	IZ	=	8.0	mm	PMID[458662]

☑ 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 NPC9436 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	88
0.1-0.2	1078
0.2-0.3	14681
0.3-0.4	20753
0.4-0.5	5738
0.5-0.6	334
0.6-0.7	15
0.7-0.8	5
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.7308	Intermediate Similarity	NPC224270
0.7037	Intermediate Similarity	NPC12727
0.6944	Remote Similarity	NPC143210
0.6303	Remote Similarity	NPC232969
0.6303	Remote Similarity	NPC199107
0.6296	Remote Similarity	NPC291712
0.6271	Remote Similarity	NPC272528
0.625	Remote Similarity	NPC24596
0.6218	Remote Similarity	NPC185929
0.6216	Remote Similarity	NPC236322
0.6204	Remote Similarity	NPC281172
0.6204	Remote Similarity	NPC2640
0.6161	Remote Similarity	NPC32944
0.6161	Remote Similarity	NPC32552
0.6161	Remote Similarity	NPC193396
0.6147	Remote Similarity	NPC472161
0.6116	Remote Similarity	NPC220730
0.6106	Remote Similarity	NPC472613
0.6087	Remote Similarity	NPC318082
0.6055	Remote Similarity	NPC475614
0.6036	Remote Similarity	NPC116231
0.6034	Remote Similarity	NPC134083
0.6018	Remote Similarity	NPC166110
0.6017	Remote Similarity	NPC34193
0.5982	Remote Similarity	NPC95364
0.5982	Remote Similarity	NPC142159
0.5965	Remote Similarity	NPC248193
0.5935	Remote Similarity	NPC472192
0.5932	Remote Similarity	NPC185253
0.5932	Remote Similarity	NPC215253
0.5882	Remote Similarity	NPC224172
0.5862	Remote Similarity	NPC31021
0.5847	Remote Similarity	NPC166770
0.5833	Remote Similarity	NPC312419
0.5798	Remote Similarity	NPC316730
0.5766	Remote Similarity	NPC296589
0.575	Remote Similarity	NPC469851
0.5736	Remote Similarity	NPC243298
0.5726	Remote Similarity	NPC471698
0.5714	Remote Similarity	NPC476141
0.5688	Remote Similarity	NPC475833
0.5664	Remote Similarity	NPC472614
0.5662	Remote Similarity	NPC163783
0.5656	Remote Similarity	NPC271059
0.5656	Remote Similarity	NPC297281
0.5656	Remote Similarity	NPC473144
0.5656	Remote Similarity	NPC318544
0.5656	Remote Similarity	NPC25666
0.5649	Remote Similarity	NPC245320
0.5635	Remote Similarity	NPC72688
0.563	Remote Similarity	NPC241426
0.563	Remote Similarity	NPC472162
0.5625	Remote Similarity	NPC470177
0.5625	Remote Similarity	NPC76283
0.5619	Remote Similarity	NPC122244
0.561	Remote Similarity	NPC470073
0.5607	Remote Similarity	NPC180290
0.5606	Remote Similarity	NPC476815
0.5606	Remote Similarity	NPC473145
0.5606	Remote Similarity	NPC31641
0.56	Remote Similarity	NPC470072

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 NPC9436 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	78
0.1-0.2	524
0.2-0.3	3900
0.3-0.4	3944
0.4-0.5	674
0.5-0.6	29
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6132	Remote Similarity	NPD5115	Clinical (unspecified phase)
0.5862	Remote Similarity	NPD5654	Approved
0.5802	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5763	Remote Similarity	NPD5959	Approved
0.5758	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5758	Remote Similarity	NPD7623	Phase 3
0.5645	Remote Similarity	NPD6614	Approved
0.5606	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.5603	Remote Similarity	NPD5694	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