NPASS Compound

Structure

CID28724 OpenBabel06191715352D 28 30 0 0 1 0 0 0 0 0999 V2000 3.4724 3.3280 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4364 1.3852 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5515 -4.0663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5515 -2.3343 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5515 -4.0663 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9627 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5588 2.9213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4543 1.9267 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0515 -1.4683 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5515 -0.6022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9915 1.9856 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4582 1.1773 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5408 1.5200 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5515 -0.6022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5515 -2.3343 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0515 -1.4683 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0515 0.2638 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9431 0.3683 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.5192 0.8002 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5515 -2.3343 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1510 1.3465 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2849 1.8465 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4068 0.3396 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0645 1.7532 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0515 -3.2003 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0515 -1.4683 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0515 -3.2003 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 7 2 0 0 0 0 2 12 1 0 0 0 0 3 25 1 0 0 0 0 4 26 1 0 0 0 0 5 27 1 0 0 0 0 6 28 1 0 0 0 0 7 8 1 0 0 0 0 8 13 1 0 0 0 0 9 14 2 0 0 0 0 9 15 1 0 0 0 0 10 14 1 0 0 0 0 10 16 2 0 0 0 0 11 13 2 0 0 0 0 11 22 1 0 0 0 0 12 17 1 0 0 0 0 12 22 1 1 0 0 0 13 19 1 0 0 0 0 15 20 2 0 0 0 0 15 25 1 0 0 0 0 16 20 1 0 0 0 0 16 26 1 0 0 0 0 17 14 1 6 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 18 21 1 0 0 0 0 19 23 1 1 0 0 0 20 27 1 0 0 0 0 21 22 1 0 0 0 0 21 24 2 0 0 0 0 22 28 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	388.19
Volume:	400.321
LogP:	2.299
LogD:	2.458
LogS:	-3.427
# Rotatable Bonds:	7
TPSA:	74.22
# H-Bond Aceptor:	6
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.724
Synthetic Accessibility Score:	5.11
Fsp3:	0.5
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.577
MDCK Permeability:	2.8362217562971637e-05
Pgp-inhibitor:	0.238
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.015
20% Bioavailability (F20%):	0.013
30% Bioavailability (F30%):	0.301

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.575
Plasma Protein Binding (PPB):	75.47225189208984%
Volume Distribution (VD):	1.118
Pgp-substrate:	19.250429153442383%

ADMET: Metabolism

CYP1A2-inhibitor:	0.022
CYP1A2-substrate:	0.968
CYP2C19-inhibitor:	0.024
CYP2C19-substrate:	0.901
CYP2C9-inhibitor:	0.018
CYP2C9-substrate:	0.172
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.373
CYP3A4-inhibitor:	0.776
CYP3A4-substrate:	0.906

ADMET: Excretion

Clearance (CL):	11.373
Half-life (T1/2):	0.519

ADMET: Toxicity

hERG Blockers:	0.011
Human Hepatotoxicity (H-HT):	0.221
Drug-inuced Liver Injury (DILI):	0.081
AMES Toxicity:	0.016
Rat Oral Acute Toxicity:	0.911
Maximum Recommended Daily Dose:	0.884
Skin Sensitization:	0.032
Carcinogencity:	0.796
Eye Corrosion:	0.004
Eye Irritation:	0.027
Respiratory Toxicity:	0.979

Download Data

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

Natural Product: NPC28724

Natural Product ID:	NPC28724
*Common Name:**	Macrophyllin B
IUPAC Name:	(2S,5S,6R,7R)-2-hydroxy-5-methoxy-6-methyl-3-prop-2-enyl-7-(3,4,5-trimethoxyphenyl)bicyclo[3.2.1]oct-3-en-8-one
Synonyms:
Standard InCHIKey:	NWXSUVZITFIXOL-FXNKJGLGSA-N
Standard InCHI:	InChI=1S/C22H28O6/c1-7-8-13-11-22(28-6)12(2)17(18(19(13)23)21(22)24)14-9-15(25-3)20(27-5)16(10-14)26-4/h7,9-12,17-19,23H,1,8H2,2-6H3/t12-,17+,18?,19-,22-/m1/s1
SMILES:	C=CCC1=C[C@]2([C@H](C)[C@@H](c3cc(c(c(c3)OC)OC)OC)C([C@@H]1O)C2=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL585912
PubChem CID:	45487148
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002341] Phenol ethers [CHEMONTID:0000138] Anisoles

*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
NPO19526	Pleurothyrium cinereum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19548690]
NPO26326	Ocotea macrophylla	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO27964	Nectandra amazonum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO19526	Pleurothyrium cinereum	Species	Lauraceae	Eukaryota	leaves	n.a.	n.a.	PMID[19880317]
NPO16019	Isodon japonica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16019	Isodon japonica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26326	Ocotea macrophylla	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27558	Podocarpus macrophyllus	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27964	Nectandra amazonum	Species	Lauraceae	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
IC50	6
Others	1

Activity Type	# Activity
Individual Protein	2
NON-MOLECULAR	3
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT324	Individual Protein	Cyclooxygenase-1	Ovis aries	IC50	=	216000.0	nM	PMID[543753]
NPT325	Individual Protein	Cyclooxygenase-2	Ovis aries	IC50	=	65400.0	nM	PMID[543753]
NPT2	Others	Unspecified		IC50	=	18900.0	nM	PMID[543753]
NPT2	Others	Unspecified		Ratio IC50	=	3.3	n.a.	PMID[543753]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	6790.0	nM	PMID[543753]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	23200.0	nM	PMID[543753]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	121000.0	nM	PMID[543753]

☑ 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 NPC28724 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	365
0.1-0.2	1294
0.2-0.3	3108
0.3-0.4	7156
0.4-0.5	11257
0.5-0.6	5268
0.6-0.7	8407
0.7-0.8	5739
0.8-0.85	86
0.85-0.9	12
0.9-0.95	4
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9412	High Similarity	NPC476244
0.9404	High Similarity	NPC476340
0.92	High Similarity	NPC476335
0.8987	High Similarity	NPC476277
0.8926	High Similarity	NPC476362
0.8867	High Similarity	NPC476338
0.8867	High Similarity	NPC476359
0.879	High Similarity	NPC476337
0.8716	High Similarity	NPC476334
0.8553	High Similarity	NPC474799
0.8535	High Similarity	NPC476363
0.8526	High Similarity	NPC327225
0.8487	Intermediate Similarity	NPC474982
0.8477	Intermediate Similarity	NPC474966
0.8471	Intermediate Similarity	NPC476364
0.8462	Intermediate Similarity	NPC151425
0.8397	Intermediate Similarity	NPC62354
0.8377	Intermediate Similarity	NPC30720
0.8375	Intermediate Similarity	NPC477410
0.8354	Intermediate Similarity	NPC25127
0.828	Intermediate Similarity	NPC178048
0.8278	Intermediate Similarity	NPC322021
0.8278	Intermediate Similarity	NPC203351
0.8269	Intermediate Similarity	NPC474903
0.8269	Intermediate Similarity	NPC472567
0.8261	Intermediate Similarity	NPC472565
0.8261	Intermediate Similarity	NPC475095
0.8258	Intermediate Similarity	NPC208507
0.8258	Intermediate Similarity	NPC472333
0.8242	Intermediate Similarity	NPC283041
0.8239	Intermediate Similarity	NPC287504
0.8224	Intermediate Similarity	NPC470991
0.8224	Intermediate Similarity	NPC19158
0.8217	Intermediate Similarity	NPC177830
0.821	Intermediate Similarity	NPC287328
0.821	Intermediate Similarity	NPC470183
0.821	Intermediate Similarity	NPC282009
0.8199	Intermediate Similarity	NPC471515
0.8199	Intermediate Similarity	NPC471479
0.8194	Intermediate Similarity	NPC212697
0.8194	Intermediate Similarity	NPC30890
0.8188	Intermediate Similarity	NPC145769
0.8182	Intermediate Similarity	NPC20237
0.8171	Intermediate Similarity	NPC476822
0.8171	Intermediate Similarity	NPC472582
0.8171	Intermediate Similarity	NPC472625
0.8166	Intermediate Similarity	NPC23593
0.8165	Intermediate Similarity	NPC163002
0.8163	Intermediate Similarity	NPC195292
0.8163	Intermediate Similarity	NPC142985
0.816	Intermediate Similarity	NPC471499
0.8148	Intermediate Similarity	NPC22192
0.8144	Intermediate Similarity	NPC279209
0.8144	Intermediate Similarity	NPC102277
0.8141	Intermediate Similarity	NPC476336
0.8137	Intermediate Similarity	NPC326037
0.8137	Intermediate Similarity	NPC320825
0.8137	Intermediate Similarity	NPC469474
0.8137	Intermediate Similarity	NPC13858
0.8137	Intermediate Similarity	NPC471500
0.8133	Intermediate Similarity	NPC150131
0.8129	Intermediate Similarity	NPC476843
0.8129	Intermediate Similarity	NPC476841
0.8121	Intermediate Similarity	NPC191930
0.8121	Intermediate Similarity	NPC62261
0.8113	Intermediate Similarity	NPC95498
0.8113	Intermediate Similarity	NPC236769
0.8113	Intermediate Similarity	NPC246566
0.8113	Intermediate Similarity	NPC56184
0.811	Intermediate Similarity	NPC472635
0.811	Intermediate Similarity	NPC48860
0.8108	Intermediate Similarity	NPC469480
0.8107	Intermediate Similarity	NPC107739
0.8105	Intermediate Similarity	NPC136649
0.8101	Intermediate Similarity	NPC475170
0.8098	Intermediate Similarity	NPC310399
0.8098	Intermediate Similarity	NPC472961
0.8098	Intermediate Similarity	NPC472962
0.8098	Intermediate Similarity	NPC73422
0.8098	Intermediate Similarity	NPC155302
0.8098	Intermediate Similarity	NPC475784
0.8098	Intermediate Similarity	NPC470326
0.8098	Intermediate Similarity	NPC161947
0.8098	Intermediate Similarity	NPC472624
0.8095	Intermediate Similarity	NPC121333
0.8089	Intermediate Similarity	NPC304821
0.8089	Intermediate Similarity	NPC294972
0.8086	Intermediate Similarity	NPC246466
0.8086	Intermediate Similarity	NPC474055
0.8086	Intermediate Similarity	NPC473272
0.8086	Intermediate Similarity	NPC284820
0.8086	Intermediate Similarity	NPC27337
0.8086	Intermediate Similarity	NPC52530
0.8086	Intermediate Similarity	NPC472598
0.8086	Intermediate Similarity	NPC67876
0.8084	Intermediate Similarity	NPC152477
0.8084	Intermediate Similarity	NPC165456
0.8075	Intermediate Similarity	NPC255807
0.8075	Intermediate Similarity	NPC226025
0.8075	Intermediate Similarity	NPC31018
0.8072	Intermediate Similarity	NPC471213
0.8072	Intermediate Similarity	NPC128293
0.807	Intermediate Similarity	NPC244903
0.807	Intermediate Similarity	NPC236089
0.8065	Intermediate Similarity	NPC27159
0.8065	Intermediate Similarity	NPC16353
0.8065	Intermediate Similarity	NPC119663
0.8063	Intermediate Similarity	NPC268992
0.8063	Intermediate Similarity	NPC473236
0.8063	Intermediate Similarity	NPC51824
0.8063	Intermediate Similarity	NPC324233
0.8063	Intermediate Similarity	NPC113608
0.8063	Intermediate Similarity	NPC470338
0.8063	Intermediate Similarity	NPC180944
0.8063	Intermediate Similarity	NPC470337
0.8063	Intermediate Similarity	NPC470340
0.8063	Intermediate Similarity	NPC323626
0.8061	Intermediate Similarity	NPC249181
0.8061	Intermediate Similarity	NPC124038
0.8061	Intermediate Similarity	NPC474240
0.8059	Intermediate Similarity	NPC263955
0.8056	Intermediate Similarity	NPC244876
0.805	Intermediate Similarity	NPC166753
0.805	Intermediate Similarity	NPC50728
0.805	Intermediate Similarity	NPC472279
0.805	Intermediate Similarity	NPC338131
0.8049	Intermediate Similarity	NPC474239
0.8049	Intermediate Similarity	NPC117985
0.8049	Intermediate Similarity	NPC201560
0.8049	Intermediate Similarity	NPC472634
0.8049	Intermediate Similarity	NPC87431
0.8049	Intermediate Similarity	NPC472632
0.8049	Intermediate Similarity	NPC173137
0.8049	Intermediate Similarity	NPC474038
0.8039	Intermediate Similarity	NPC147379
0.8039	Intermediate Similarity	NPC474784
0.8038	Intermediate Similarity	NPC261548
0.8038	Intermediate Similarity	NPC125570
0.8037	Intermediate Similarity	NPC55738
0.8037	Intermediate Similarity	NPC473990
0.8037	Intermediate Similarity	NPC209473
0.8037	Intermediate Similarity	NPC152904
0.8037	Intermediate Similarity	NPC329743
0.8026	Intermediate Similarity	NPC477938
0.8025	Intermediate Similarity	NPC317383
0.8025	Intermediate Similarity	NPC470762
0.8025	Intermediate Similarity	NPC303255
0.8025	Intermediate Similarity	NPC250922
0.8025	Intermediate Similarity	NPC474167
0.8025	Intermediate Similarity	NPC278778
0.8025	Intermediate Similarity	NPC316769
0.8025	Intermediate Similarity	NPC12377
0.8025	Intermediate Similarity	NPC195796
0.8025	Intermediate Similarity	NPC35038
0.8025	Intermediate Similarity	NPC291878
0.8024	Intermediate Similarity	NPC158761
0.8024	Intermediate Similarity	NPC470456
0.8013	Intermediate Similarity	NPC301751
0.8013	Intermediate Similarity	NPC245482
0.8013	Intermediate Similarity	NPC470990
0.8012	Intermediate Similarity	NPC270620
0.8012	Intermediate Similarity	NPC29587
0.8012	Intermediate Similarity	NPC475888
0.8012	Intermediate Similarity	NPC18727
0.8012	Intermediate Similarity	NPC78326
0.8012	Intermediate Similarity	NPC234052
0.8012	Intermediate Similarity	NPC470457
0.8012	Intermediate Similarity	NPC224280
0.8012	Intermediate Similarity	NPC236223
0.8012	Intermediate Similarity	NPC179126
0.8	Intermediate Similarity	NPC256406
0.8	Intermediate Similarity	NPC76376
0.8	Intermediate Similarity	NPC474034
0.8	Intermediate Similarity	NPC262623
0.8	Intermediate Similarity	NPC273657
0.8	Intermediate Similarity	NPC125991
0.8	Intermediate Similarity	NPC472964
0.8	Intermediate Similarity	NPC106920
0.8	Intermediate Similarity	NPC211107
0.8	Intermediate Similarity	NPC474150
0.8	Intermediate Similarity	NPC474162
0.8	Intermediate Similarity	NPC474033
0.7988	Intermediate Similarity	NPC472630
0.7988	Intermediate Similarity	NPC174953
0.7988	Intermediate Similarity	NPC472902
0.7988	Intermediate Similarity	NPC299436
0.7988	Intermediate Similarity	NPC263449
0.7988	Intermediate Similarity	NPC472631
0.7988	Intermediate Similarity	NPC192686
0.7988	Intermediate Similarity	NPC119209
0.7988	Intermediate Similarity	NPC328102
0.7988	Intermediate Similarity	NPC118256
0.7988	Intermediate Similarity	NPC36217
0.7987	Intermediate Similarity	NPC159103
0.7987	Intermediate Similarity	NPC474017
0.7987	Intermediate Similarity	NPC12854
0.7987	Intermediate Similarity	NPC51681
0.7976	Intermediate Similarity	NPC242395
0.7975	Intermediate Similarity	NPC299520
0.7975	Intermediate Similarity	NPC179732

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 NPC28724 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	314
0.1-0.2	847
0.2-0.3	1843
0.3-0.4	2646
0.4-0.5	1927
0.5-0.6	1087
0.6-0.7	410
0.7-0.8	76
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
0.8025	Intermediate Similarity	NPD3882	Suspended
0.7952	Intermediate Similarity	NPD7184	Clinical (unspecified phase)
0.795	Intermediate Similarity	NPD37	Approved
0.795	Intermediate Similarity	NPD1934	Approved
0.7904	Intermediate Similarity	NPD6168	Clinical (unspecified phase)
0.7904	Intermediate Similarity	NPD6167	Clinical (unspecified phase)
0.7904	Intermediate Similarity	NPD6166	Phase 2
0.7901	Intermediate Similarity	NPD2393	Clinical (unspecified phase)
0.7853	Intermediate Similarity	NPD3817	Phase 2
0.7852	Intermediate Similarity	NPD3027	Phase 3
0.7831	Intermediate Similarity	NPD7199	Phase 2
0.7805	Intermediate Similarity	NPD4965	Approved
0.7805	Intermediate Similarity	NPD4966	Approved
0.7805	Intermediate Similarity	NPD4967	Phase 2
0.7771	Intermediate Similarity	NPD5494	Approved
0.7683	Intermediate Similarity	NPD2801	Approved
0.7647	Intermediate Similarity	NPD7473	Discontinued
0.7625	Intermediate Similarity	NPD4378	Clinical (unspecified phase)
0.7607	Intermediate Similarity	NPD4380	Phase 2
0.7605	Intermediate Similarity	NPD6234	Discontinued
0.7602	Intermediate Similarity	NPD3818	Discontinued
0.7586	Intermediate Similarity	NPD7808	Phase 3
0.7578	Intermediate Similarity	NPD1512	Approved
0.7576	Intermediate Similarity	NPD7096	Clinical (unspecified phase)
0.7574	Intermediate Similarity	NPD6232	Discontinued
0.7572	Intermediate Similarity	NPD6797	Phase 2
0.7557	Intermediate Similarity	NPD8055	Clinical (unspecified phase)
0.7545	Intermediate Similarity	NPD7075	Discontinued
0.7529	Intermediate Similarity	NPD7251	Discontinued
0.7516	Intermediate Similarity	NPD5762	Approved
0.7516	Intermediate Similarity	NPD5763	Approved
0.7515	Intermediate Similarity	NPD1247	Approved
0.7515	Intermediate Similarity	NPD6801	Discontinued
0.7514	Intermediate Similarity	NPD7074	Phase 3
0.75	Intermediate Similarity	NPD7028	Phase 2
0.75	Intermediate Similarity	NPD919	Approved
0.7486	Intermediate Similarity	NPD4338	Clinical (unspecified phase)
0.7471	Intermediate Similarity	NPD3787	Discontinued
0.7457	Intermediate Similarity	NPD7054	Approved
0.7457	Intermediate Similarity	NPD5844	Phase 1
0.7453	Intermediate Similarity	NPD6799	Approved
0.7453	Intermediate Similarity	NPD1511	Approved
0.7419	Intermediate Similarity	NPD6355	Discontinued
0.7414	Intermediate Similarity	NPD7472	Approved
0.7405	Intermediate Similarity	NPD6005	Phase 3
0.7405	Intermediate Similarity	NPD6003	Clinical (unspecified phase)
0.7405	Intermediate Similarity	NPD6002	Phase 3
0.7405	Intermediate Similarity	NPD6004	Phase 3
0.7405	Intermediate Similarity	NPD6006	Clinical (unspecified phase)
0.7399	Intermediate Similarity	NPD3751	Discontinued
0.7399	Intermediate Similarity	NPD7228	Approved
0.7394	Intermediate Similarity	NPD6599	Discontinued
0.7389	Intermediate Similarity	NPD1510	Phase 2
0.7358	Intermediate Similarity	NPD970	Clinical (unspecified phase)
0.7356	Intermediate Similarity	NPD7804	Clinical (unspecified phase)
0.7355	Intermediate Similarity	NPD3620	Phase 2
0.7355	Intermediate Similarity	NPD1613	Approved
0.7355	Intermediate Similarity	NPD1240	Approved
0.7355	Intermediate Similarity	NPD3619	Clinical (unspecified phase)
0.7355	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7342	Intermediate Similarity	NPD6099	Approved
0.7342	Intermediate Similarity	NPD6100	Approved
0.7338	Intermediate Similarity	NPD6859	Clinical (unspecified phase)
0.733	Intermediate Similarity	NPD7685	Pre-registration
0.7329	Intermediate Similarity	NPD6190	Approved
0.7326	Intermediate Similarity	NPD3926	Phase 2
0.7321	Intermediate Similarity	NPD8443	Clinical (unspecified phase)
0.7317	Intermediate Similarity	NPD6980	Clinical (unspecified phase)
0.731	Intermediate Similarity	NPD8127	Discontinued
0.7303	Intermediate Similarity	NPD5647	Approved
0.7301	Intermediate Similarity	NPD2532	Approved
0.7301	Intermediate Similarity	NPD2534	Approved
0.7301	Intermediate Similarity	NPD2533	Approved
0.7296	Intermediate Similarity	NPD1552	Clinical (unspecified phase)
0.7296	Intermediate Similarity	NPD1550	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD4868	Clinical (unspecified phase)
0.7278	Intermediate Similarity	NPD7033	Discontinued
0.7267	Intermediate Similarity	NPD4109	Clinical (unspecified phase)
0.7267	Intermediate Similarity	NPD4110	Phase 3
0.7262	Intermediate Similarity	NPD7819	Suspended
0.7261	Intermediate Similarity	NPD1607	Approved
0.7261	Intermediate Similarity	NPD6653	Approved
0.725	Intermediate Similarity	NPD1549	Phase 2
0.7239	Intermediate Similarity	NPD6143	Clinical (unspecified phase)
0.7235	Intermediate Similarity	NPD4381	Clinical (unspecified phase)
0.7233	Intermediate Similarity	NPD2796	Approved
0.7219	Intermediate Similarity	NPD5402	Approved
0.7205	Intermediate Similarity	NPD2800	Approved
0.7195	Intermediate Similarity	NPD7004	Clinical (unspecified phase)
0.719	Intermediate Similarity	NPD6917	Clinical (unspecified phase)
0.7175	Intermediate Similarity	NPD7993	Clinical (unspecified phase)
0.716	Intermediate Similarity	NPD5761	Phase 2
0.716	Intermediate Similarity	NPD5760	Phase 2
0.716	Intermediate Similarity	NPD6398	Clinical (unspecified phase)
0.7152	Intermediate Similarity	NPD6651	Approved
0.7135	Intermediate Similarity	NPD7240	Approved
0.7127	Intermediate Similarity	NPD8434	Phase 2
0.7115	Intermediate Similarity	NPD6410	Clinical (unspecified phase)
0.711	Intermediate Similarity	NPD6959	Discontinued
0.7108	Intermediate Similarity	NPD5403	Approved
0.7097	Intermediate Similarity	NPD1529	Clinical (unspecified phase)
0.7091	Intermediate Similarity	NPD7410	Clinical (unspecified phase)
0.7089	Intermediate Similarity	NPD230	Phase 1
0.7086	Intermediate Similarity	NPD2403	Approved
0.7063	Intermediate Similarity	NPD651	Clinical (unspecified phase)
0.7055	Intermediate Similarity	NPD4628	Phase 3
0.7055	Intermediate Similarity	NPD5283	Phase 1
0.7041	Intermediate Similarity	NPD7411	Suspended
0.7039	Intermediate Similarity	NPD6559	Discontinued
0.7039	Intermediate Similarity	NPD6764	Approved
0.7039	Intermediate Similarity	NPD6765	Approved
0.7032	Intermediate Similarity	NPD1530	Clinical (unspecified phase)
0.7032	Intermediate Similarity	NPD2861	Phase 2
0.7032	Intermediate Similarity	NPD3018	Phase 2
0.7025	Intermediate Similarity	NPD943	Approved
0.7025	Intermediate Similarity	NPD4060	Phase 1
0.7019	Intermediate Similarity	NPD2935	Discontinued
0.7006	Intermediate Similarity	NPD6798	Discontinued
0.7006	Intermediate Similarity	NPD4907	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD4749	Approved
0.6993	Remote Similarity	NPD4379	Clinical (unspecified phase)
0.6993	Remote Similarity	NPD2983	Phase 2
0.6993	Remote Similarity	NPD2982	Phase 2
0.6988	Remote Similarity	NPD5401	Approved
0.6987	Remote Similarity	NPD4908	Phase 1
0.6973	Remote Similarity	NPD7879	Clinical (unspecified phase)
0.6971	Remote Similarity	NPD7229	Phase 3
0.697	Remote Similarity	NPD7236	Approved
0.6962	Remote Similarity	NPD6233	Phase 2
0.6951	Remote Similarity	NPD1878	Clinical (unspecified phase)
0.6933	Remote Similarity	NPD2424	Discontinued
0.6928	Remote Similarity	NPD2981	Phase 2
0.6928	Remote Similarity	NPD1608	Approved
0.6928	Remote Similarity	NPD4357	Discontinued
0.6923	Remote Similarity	NPD9494	Approved
0.6919	Remote Similarity	NPD5353	Approved
0.6918	Remote Similarity	NPD4140	Approved
0.6915	Remote Similarity	NPD2974	Approved
0.6915	Remote Similarity	NPD2975	Approved
0.6915	Remote Similarity	NPD2973	Approved
0.6895	Remote Similarity	NPD4580	Approved
0.6886	Remote Similarity	NPD3688	Clinical (unspecified phase)
0.6886	Remote Similarity	NPD3146	Approved
0.6885	Remote Similarity	NPD6785	Approved
0.6885	Remote Similarity	NPD6784	Approved
0.6875	Remote Similarity	NPD5124	Phase 1
0.6875	Remote Similarity	NPD3657	Discovery
0.6875	Remote Similarity	NPD447	Suspended
0.6875	Remote Similarity	NPD5735	Approved
0.6875	Remote Similarity	NPD5123	Clinical (unspecified phase)
0.6867	Remote Similarity	NPD5536	Phase 2
0.6864	Remote Similarity	NPD1653	Approved
0.6863	Remote Similarity	NPD3705	Approved
0.6863	Remote Similarity	NPD1610	Phase 2
0.686	Remote Similarity	NPD1465	Phase 2
0.6859	Remote Similarity	NPD2493	Approved
0.6859	Remote Similarity	NPD2494	Approved
0.6859	Remote Similarity	NPD4624	Approved
0.6848	Remote Similarity	NPD3750	Approved
0.6845	Remote Similarity	NPD6273	Approved
0.6842	Remote Similarity	NPD5090	Approved
0.6842	Remote Similarity	NPD5089	Approved
0.6842	Remote Similarity	NPD7615	Clinical (unspecified phase)
0.6842	Remote Similarity	NPD2932	Approved
0.6839	Remote Similarity	NPD7975	Clinical (unspecified phase)
0.6839	Remote Similarity	NPD4583	Approved
0.6839	Remote Similarity	NPD4582	Approved
0.6836	Remote Similarity	NPD5242	Approved
0.6835	Remote Similarity	NPD7095	Approved
0.6829	Remote Similarity	NPD5958	Discontinued
0.6816	Remote Similarity	NPD7799	Discontinued
0.6813	Remote Similarity	NPD2238	Phase 2
0.6813	Remote Similarity	NPD4419	Clinical (unspecified phase)
0.681	Remote Similarity	NPD5712	Approved
0.6805	Remote Similarity	NPD920	Approved
0.6803	Remote Similarity	NPD228	Approved
0.6798	Remote Similarity	NPD7852	Clinical (unspecified phase)
0.6795	Remote Similarity	NPD6362	Approved
0.6795	Remote Similarity	NPD3094	Phase 2
0.6788	Remote Similarity	NPD4004	Approved
0.6788	Remote Similarity	NPD4002	Approved
0.6788	Remote Similarity	NPD7421	Clinical (unspecified phase)
0.6782	Remote Similarity	NPD7768	Phase 2
0.678	Remote Similarity	NPD5711	Approved
0.678	Remote Similarity	NPD5710	Approved
0.6776	Remote Similarity	NPD1357	Approved
0.6776	Remote Similarity	NPD1651	Approved
0.6774	Remote Similarity	NPD8397	Clinical (unspecified phase)
0.6771	Remote Similarity	NPD3452	Approved
0.6771	Remote Similarity	NPD3450	Approved
0.6765	Remote Similarity	NPD7239	Suspended
0.6757	Remote Similarity	NPD8150	Discontinued
0.675	Remote Similarity	NPD6663	Approved
0.675	Remote Similarity	NPD4062	Phase 3
0.6747	Remote Similarity	NPD3892	Phase 2
0.6743	Remote Similarity	NPD3749	Approved
0.6739	Remote Similarity	NPD7090	Clinical (unspecified phase)
0.6738	Remote Similarity	NPD2488	Approved
0.6738	Remote Similarity	NPD2490	Approved
0.6732	Remote Similarity	NPD3019	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