NPASS Compound

Structure

NPC161644 OpenBabel07101719512D 41 45 0 0 1 0 0 0 0 0999 V2000 -2.4337 2.8759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5676 5.3759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2997 -0.6241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7686 1.3320 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6285 -0.6241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9757 -1.4311 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4337 3.8759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0259 1.1031 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1644 -0.6241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8965 2.3759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1644 2.3759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5676 4.3759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4337 -0.1241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0576 0.7687 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7016 -0.1241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3890 0.6689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7625 0.8759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0304 -0.1241 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.8965 1.3759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1644 1.3759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7016 0.8759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3314 -0.0998 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8965 -0.6241 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5676 -0.6241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7521 1.1031 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4337 0.8759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5676 1.3759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6369 -0.4342 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7016 3.8759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8965 3.3759 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.7625 -0.1241 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0304 0.8759 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -1.5676 -1.6241 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8268 2.1003 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2997 1.3759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5676 2.3759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5622 -1.4314 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1644 4.3759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9010 -0.4339 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7016 2.8759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 7 1 0 0 0 0 2 12 1 0 0 0 0 3 13 1 0 0 0 0 4 14 1 0 0 0 0 5 32 1 0 0 0 0 6 40 1 0 0 0 0 7 12 2 0 0 0 0 8 16 1 0 0 0 0 9 15 1 0 0 0 0 9 18 1 0 0 0 0 10 19 1 0 0 0 0 10 31 3 0 0 0 0 11 20 1 0 0 0 0 11 41 1 0 0 0 0 12 30 1 0 0 0 0 13 24 1 0 0 0 0 13 26 2 0 0 0 0 14 25 1 0 0 0 0 14 29 2 0 0 0 0 15 21 2 0 0 0 0 15 24 1 0 0 0 0 16 22 2 0 0 0 0 16 25 1 0 0 0 0 17 8 1 6 0 0 0 17 19 1 0 0 0 0 17 32 1 0 0 0 0 18 23 1 0 0 0 0 18 33 1 6 0 0 0 19 33 1 1 0 0 0 20 21 1 0 0 0 0 20 33 1 6 0 0 0 21 27 1 0 0 0 0 22 28 1 0 0 0 0 23 22 1 6 0 0 0 23 32 1 0 0 0 0 24 34 2 0 0 0 0 25 35 2 0 0 0 0 26 27 1 0 0 0 0 26 36 1 0 0 0 0 27 37 2 0 0 0 0 28 29 1 0 0 0 0 28 38 2 0 0 0 0 29 40 1 0 0 0 0 30 39 2 0 0 0 0 30 41 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	561.21
Volume:	556.328
LogP:	4.387
LogD:	2.393
LogS:	-3.479
# Rotatable Bonds:	4
TPSA:	166.95
# H-Bond Aceptor:	11
# H-Bond Donor:	5
# Rings:	5
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.122
Synthetic Accessibility Score:	5.626
Fsp3:	0.333
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	2
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.829
MDCK Permeability:	1.3703343029192183e-05
Pgp-inhibitor:	0.609
Pgp-substrate:	0.971
Human Intestinal Absorption (HIA):	0.949
20% Bioavailability (F20%):	0.944
30% Bioavailability (F30%):	0.421

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004
Plasma Protein Binding (PPB):	94.49927520751953%
Volume Distribution (VD):	0.857
Pgp-substrate:	8.142524719238281%

ADMET: Metabolism

CYP1A2-inhibitor:	0.028
CYP1A2-substrate:	0.342
CYP2C19-inhibitor:	0.068
CYP2C19-substrate:	0.08
CYP2C9-inhibitor:	0.852
CYP2C9-substrate:	0.787
CYP2D6-inhibitor:	0.2
CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.288
CYP3A4-substrate:	0.917

ADMET: Excretion

Clearance (CL):	7.425
Half-life (T1/2):	0.821

ADMET: Toxicity

hERG Blockers:	0.014
Human Hepatotoxicity (H-HT):	0.837
Drug-inuced Liver Injury (DILI):	0.974
AMES Toxicity:	0.051
Rat Oral Acute Toxicity:	0.744
Maximum Recommended Daily Dose:	0.643
Skin Sensitization:	0.947
Carcinogencity:	0.226
Eye Corrosion:	0.003
Eye Irritation:	0.107
Respiratory Toxicity:	0.804

Download Data

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

Natural Product: NPC161644

Natural Product ID:	NPC161644
*Common Name:**	Renieramycin S
IUPAC Name:	n.a.
Synonyms:	Renieramycin S
Standard InCHIKey:	FSDHSSHYVUZGFT-INUIFXHSSA-N
Standard InCHI:	InChI=1S/C30H31N3O8/c1-7-12(2)30(39)41-11-20-21-15(24(34)13(3)26(36)27(21)37)9-18-23-22-16(25(35)14(4)29(40-6)28(22)38)8-17(32(23)5)19(10-31)33(18)20/h7,17-20,23,36H,8-9,11H2,1-6H3/b12-7-/t17-,18-,19-,20-,23-/m0/s1
SMILES:	C/C=C(/C)C(=O)OC[C@H]1C2=C(C[C@H]3[C@H]4C5=C(C[C@@H]([C@H](C#N)N13)N4C)C(=O)C(=C(C5=O)OC)C)C(=O)C(=C(C2=O)O)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL468488
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives [CHEMONTID:0002567] Isoquinoline quinones

*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
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11908959]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Caledonian	n.a.	PMID[1453184]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Thai	n.a.	PMID[14640515]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	thai	n.a.	PMID[15217287]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1710256]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesia	n.a.	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	coral reef habitat at a depth of approximately 20 m from the sea bed surface, at Sangalaki, Indonesia (2 04 59 N, 118 23 41 E)	1996-MAR	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[31260310]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Philippine	n.a.	PMID[7473578]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7798966]

☑ 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
IC50	2

Activity Type	# Activity
Cell Line	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	15.0	nM	PMID[458212]
NPT3558	Cell Line	QG-56		IC50	=	26.0	nM	PMID[458212]

☑ 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 NPC161644 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	134
0.1-0.2	1000
0.2-0.3	7195
0.3-0.4	23471
0.4-0.5	10228
0.5-0.6	653
0.6-0.7	5
0.7-0.8	5
0.8-0.85	0
0.85-0.9	1
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9669	High Similarity	NPC97861
0.9449	High Similarity	NPC25025
0.9286	High Similarity	NPC473703
0.9286	High Similarity	NPC239252
0.7536	Intermediate Similarity	NPC313348
0.7536	Intermediate Similarity	NPC475987
0.7424	Intermediate Similarity	NPC315110
0.7293	Intermediate Similarity	NPC13351
0.7273	Intermediate Similarity	NPC473955
0.6288	Remote Similarity	NPC469895
0.6267	Remote Similarity	NPC82129
0.6107	Remote Similarity	NPC120335
0.6084	Remote Similarity	NPC230849
0.6012	Remote Similarity	NPC475342
0.6	Remote Similarity	NPC315011
0.5946	Remote Similarity	NPC247902
0.5946	Remote Similarity	NPC262880
0.5944	Remote Similarity	NPC471673
0.592	Remote Similarity	NPC296589
0.5912	Remote Similarity	NPC271562
0.5909	Remote Similarity	NPC241426
0.5882	Remote Similarity	NPC133420
0.5879	Remote Similarity	NPC44040
0.5878	Remote Similarity	NPC309525
0.5862	Remote Similarity	NPC11379
0.5857	Remote Similarity	NPC181510
0.5857	Remote Similarity	NPC168758
0.5857	Remote Similarity	NPC47857
0.5833	Remote Similarity	NPC174463
0.5833	Remote Similarity	NPC235625
0.5828	Remote Similarity	NPC215507
0.5828	Remote Similarity	NPC41162
0.5827	Remote Similarity	NPC298484
0.5806	Remote Similarity	NPC45813
0.5775	Remote Similarity	NPC130124
0.5775	Remote Similarity	NPC193471
0.5762	Remote Similarity	NPC470539
0.5758	Remote Similarity	NPC475180
0.5758	Remote Similarity	NPC150041
0.5753	Remote Similarity	NPC88190
0.5752	Remote Similarity	NPC133089
0.5736	Remote Similarity	NPC473746
0.5724	Remote Similarity	NPC120599
0.5724	Remote Similarity	NPC200412
0.5724	Remote Similarity	NPC156336
0.5714	Remote Similarity	NPC120420
0.5705	Remote Similarity	NPC97580
0.5695	Remote Similarity	NPC173173
0.5694	Remote Similarity	NPC288629
0.5677	Remote Similarity	NPC99864
0.5674	Remote Similarity	NPC196073
0.5674	Remote Similarity	NPC195435
0.5672	Remote Similarity	NPC476344
0.5672	Remote Similarity	NPC265662
0.5672	Remote Similarity	NPC472167
0.5652	Remote Similarity	NPC211215
0.5643	Remote Similarity	NPC470535
0.5629	Remote Similarity	NPC476951
0.5629	Remote Similarity	NPC317654
0.5629	Remote Similarity	NPC96010
0.5625	Remote Similarity	NPC469861
0.5625	Remote Similarity	NPC130436
0.5625	Remote Similarity	NPC272166
0.5625	Remote Similarity	NPC469860
0.5621	Remote Similarity	NPC307165
0.562	Remote Similarity	NPC473289
0.5616	Remote Similarity	NPC470300
0.5616	Remote Similarity	NPC106791
0.5616	Remote Similarity	NPC201889
0.5616	Remote Similarity	NPC284656
0.5616	Remote Similarity	NPC476952
0.5612	Remote Similarity	NPC93179
0.5608	Remote Similarity	NPC23963
0.5603	Remote Similarity	NPC470536
0.56	Remote Similarity	NPC469999

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 NPC161644 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	104
0.1-0.2	698
0.2-0.3	3033
0.3-0.4	4086
0.4-0.5	1166
0.5-0.6	60
0.6-0.7	2
0.7-0.8	1
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
0.7424	Intermediate Similarity	NPD7196	Clinical (unspecified phase)
0.6288	Remote Similarity	NPD2259	Approved
0.6288	Remote Similarity	NPD2258	Approved
0.6	Remote Similarity	NPD2101	Approved
0.5986	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.5789	Remote Similarity	NPD7260	Phase 2
0.5742	Remote Similarity	NPD8387	Clinical (unspecified phase)
0.5677	Remote Similarity	NPD8415	Approved
0.5676	Remote Similarity	NPD2838	Clinical (unspecified phase)
0.5649	Remote Similarity	NPD6845	Suspended
0.5625	Remote Similarity	NPD1000	Clinical (unspecified phase)

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