NPASS Compound

Structure

NPC21667 OpenBabel07101718322D 23 26 0 0 1 0 0 0 0 0999 V2000 4.8363 2.9680 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 2.1913 2.4135 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 1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1369 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5491 0.1910 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 1.7321 2.0000 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 3.8581 2.7601 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 -1.7321 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5491 1.8090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1890 3.5032 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 13 1 0 0 0 0 4 5 1 0 0 0 0 4 14 2 0 0 0 0 6 7 1 0 0 0 0 6 17 1 0 0 0 0 7 18 1 0 0 0 0 8 10 1 0 0 0 0 8 15 1 0 0 0 0 9 11 1 0 0 0 0 9 19 1 0 0 0 0 10 20 1 0 0 0 0 11 21 1 0 0 0 0 12 14 1 0 0 0 0 12 15 1 0 0 0 0 13 17 1 0 0 0 0 13 23 2 0 0 0 0 14 20 1 0 0 0 0 15 22 1 6 0 0 0 16 5 1 6 0 0 0 16 18 1 0 0 0 0 16 19 1 0 0 0 0 17 21 1 1 0 0 0 18 21 1 1 0 0 0 19 20 1 1 0 0 0 20 2 1 1 0 0 0 21 3 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	315.26
Volume:	352.06
LogP:	4.053
LogD:	3.987
LogS:	-4.132
# Rotatable Bonds:	1
TPSA:	43.09
# H-Bond Aceptor:	2
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	2

MedChem Properties

QED Drug-Likeness Score:	0.725
Synthetic Accessibility Score:	4.207
Fsp3:	0.857
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.656
MDCK Permeability:	1.0940237189061008e-05
Pgp-inhibitor:	0.007
Pgp-substrate:	0.009
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.698
30% Bioavailability (F30%):	0.029

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.772
Plasma Protein Binding (PPB):	86.01300811767578%
Volume Distribution (VD):	1.088
Pgp-substrate:	8.253762245178223%

ADMET: Metabolism

CYP1A2-inhibitor:	0.345
CYP1A2-substrate:	0.259
CYP2C19-inhibitor:	0.141
CYP2C19-substrate:	0.801
CYP2C9-inhibitor:	0.195
CYP2C9-substrate:	0.061
CYP2D6-inhibitor:	0.864
CYP2D6-substrate:	0.903
CYP3A4-inhibitor:	0.715
CYP3A4-substrate:	0.329

ADMET: Excretion

Clearance (CL):	17.901
Half-life (T1/2):	0.08

ADMET: Toxicity

hERG Blockers:	0.566
Human Hepatotoxicity (H-HT):	0.36
Drug-inuced Liver Injury (DILI):	0.817
AMES Toxicity:	0.006
Rat Oral Acute Toxicity:	0.821
Maximum Recommended Daily Dose:	0.894
Skin Sensitization:	0.918
Carcinogencity:	0.596
Eye Corrosion:	0.499
Eye Irritation:	0.027
Respiratory Toxicity:	0.98

Download Data

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

Natural Product: NPC21667

Natural Product ID:	NPC21667
*Common Name:**	Holamine
IUPAC Name:	1-[(3R,8S,9S,10R,13S,14S,17S)-3-amino-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
Synonyms:	Holamine
Standard InCHIKey:	GPRZXDPWGLHIQE-QYYVTAPASA-N
Standard InCHI:	InChI=1S/C21H33NO/c1-13(23)17-6-7-18-16-5-4-14-12-15(22)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19H,5-12,22H2,1-3H3/t15-,16+,17-,18+,19+,20+,21-/m1/s1
SMILES:	N[C@@H]1CC[C@]2(C(=CC[C@@H]3[C@@H]2CC[C@]2([C@H]3CC[C@@H]2C(=O)C)C)C1)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL465586
PubChem CID:	12310548
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003569] Pregnane steroids

*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
NPO32911	holarrhena curtisii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9834146]

☑ 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	5

Activity Type	# Activity
Cell Line	4
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	0.2	ug.mL-1	PMID[493697]
NPT168	Cell Line	P388	Mus musculus	IC50	=	0.91	ug.mL-1	PMID[493697]
NPT168	Cell Line	P388	Mus musculus	IC50	=	0.85	ug.mL-1	PMID[493697]
NPT168	Cell Line	P388	Mus musculus	IC50	=	0.83	ug.mL-1	PMID[493697]
NPT633	Organism	Leishmania donovani	Leishmania donovani	IC50	=	0.39	ug.mL-1	PMID[493697]

☑ 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 NPC21667 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	101
0.1-0.2	1201
0.2-0.3	16544
0.3-0.4	13023
0.4-0.5	7674
0.5-0.6	3472
0.6-0.7	593
0.7-0.8	75
0.8-0.85	13
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8427	Intermediate Similarity	NPC476754
0.8315	Intermediate Similarity	NPC476752
0.8315	Intermediate Similarity	NPC476753
0.8191	Intermediate Similarity	NPC58200
0.8182	Intermediate Similarity	NPC20610
0.814	Intermediate Similarity	NPC182106
0.814	Intermediate Similarity	NPC311769
0.8105	Intermediate Similarity	NPC98765
0.8101	Intermediate Similarity	NPC110615
0.8077	Intermediate Similarity	NPC182815
0.7979	Intermediate Similarity	NPC239768
0.7979	Intermediate Similarity	NPC128698
0.7978	Intermediate Similarity	NPC249312
0.7975	Intermediate Similarity	NPC282593
0.7975	Intermediate Similarity	NPC159577
0.7975	Intermediate Similarity	NPC35734
0.7938	Intermediate Similarity	NPC230677
0.7875	Intermediate Similarity	NPC115023
0.7875	Intermediate Similarity	NPC470078
0.7865	Intermediate Similarity	NPC259252
0.7778	Intermediate Similarity	NPC251705
0.7778	Intermediate Similarity	NPC303613
0.7778	Intermediate Similarity	NPC474228
0.7755	Intermediate Similarity	NPC233256
0.7755	Intermediate Similarity	NPC195841
0.775	Intermediate Similarity	NPC307176
0.775	Intermediate Similarity	NPC477856
0.775	Intermediate Similarity	NPC214770
0.7692	Intermediate Similarity	NPC323005
0.7684	Intermediate Similarity	NPC140685
0.7654	Intermediate Similarity	NPC234707
0.7625	Intermediate Similarity	NPC139397
0.759	Intermediate Similarity	NPC293803
0.7586	Intermediate Similarity	NPC215474
0.7561	Intermediate Similarity	NPC470044
0.7561	Intermediate Similarity	NPC470045
0.7558	Intermediate Similarity	NPC12035
0.7531	Intermediate Similarity	NPC40574
0.7531	Intermediate Similarity	NPC251929
0.7531	Intermediate Similarity	NPC2634
0.7531	Intermediate Similarity	NPC260040
0.7531	Intermediate Similarity	NPC265782
0.75	Intermediate Similarity	NPC69408
0.7471	Intermediate Similarity	NPC329782
0.7471	Intermediate Similarity	NPC152039
0.7471	Intermediate Similarity	NPC118329
0.747	Intermediate Similarity	NPC255021
0.747	Intermediate Similarity	NPC309852
0.7449	Intermediate Similarity	NPC152718
0.7439	Intermediate Similarity	NPC54123
0.7439	Intermediate Similarity	NPC21773
0.7439	Intermediate Similarity	NPC305501
0.7436	Intermediate Similarity	NPC469662
0.7386	Intermediate Similarity	NPC472312
0.7386	Intermediate Similarity	NPC283277
0.7353	Intermediate Similarity	NPC175585
0.7326	Intermediate Similarity	NPC82635
0.7326	Intermediate Similarity	NPC470052
0.7308	Intermediate Similarity	NPC202118
0.7308	Intermediate Similarity	NPC197238
0.7284	Intermediate Similarity	NPC39157
0.7284	Intermediate Similarity	NPC82477
0.7284	Intermediate Similarity	NPC296697
0.7284	Intermediate Similarity	NPC142754
0.7273	Intermediate Similarity	NPC226509
0.7262	Intermediate Similarity	NPC476904
0.725	Intermediate Similarity	NPC189917
0.725	Intermediate Similarity	NPC43300
0.725	Intermediate Similarity	NPC96812
0.725	Intermediate Similarity	NPC107704
0.725	Intermediate Similarity	NPC39462
0.725	Intermediate Similarity	NPC168824
0.7241	Intermediate Similarity	NPC211322
0.7216	Intermediate Similarity	NPC184033
0.7209	Intermediate Similarity	NPC91665
0.7195	Intermediate Similarity	NPC286814
0.7176	Intermediate Similarity	NPC473171
0.7176	Intermediate Similarity	NPC255650
0.716	Intermediate Similarity	NPC220210
0.716	Intermediate Similarity	NPC176107
0.716	Intermediate Similarity	NPC20181
0.7159	Intermediate Similarity	NPC474509
0.7143	Intermediate Similarity	NPC24733
0.7129	Intermediate Similarity	NPC119329
0.7129	Intermediate Similarity	NPC469958
0.7128	Intermediate Similarity	NPC84171
0.7093	Intermediate Similarity	NPC7214
0.7079	Intermediate Similarity	NPC147066
0.7079	Intermediate Similarity	NPC474122
0.7059	Intermediate Similarity	NPC474797
0.7059	Intermediate Similarity	NPC474796
0.7059	Intermediate Similarity	NPC329866
0.7045	Intermediate Similarity	NPC215843
0.7045	Intermediate Similarity	NPC90965
0.7045	Intermediate Similarity	NPC170793
0.7037	Intermediate Similarity	NPC92327
0.7024	Intermediate Similarity	NPC265789
0.7024	Intermediate Similarity	NPC223187
0.7024	Intermediate Similarity	NPC190035
0.7011	Intermediate Similarity	NPC470557
0.7	Intermediate Similarity	NPC320514
0.7	Intermediate Similarity	NPC472239
0.7	Intermediate Similarity	NPC474001
0.7	Intermediate Similarity	NPC34193
0.699	Remote Similarity	NPC476756
0.699	Remote Similarity	NPC244982
0.6989	Remote Similarity	NPC43308
0.6988	Remote Similarity	NPC477857
0.6962	Remote Similarity	NPC213152
0.6962	Remote Similarity	NPC60565
0.6957	Remote Similarity	NPC147513
0.6957	Remote Similarity	NPC75810
0.6941	Remote Similarity	NPC474488
0.6939	Remote Similarity	NPC247220
0.6932	Remote Similarity	NPC469996
0.6923	Remote Similarity	NPC470046
0.6923	Remote Similarity	NPC470047
0.6909	Remote Similarity	NPC35037
0.6889	Remote Similarity	NPC201912
0.6889	Remote Similarity	NPC4166
0.6889	Remote Similarity	NPC38350
0.6883	Remote Similarity	NPC230823
0.6883	Remote Similarity	NPC49575
0.6883	Remote Similarity	NPC267626
0.6883	Remote Similarity	NPC55004
0.6882	Remote Similarity	NPC157479
0.6875	Remote Similarity	NPC165695
0.6869	Remote Similarity	NPC167419
0.6869	Remote Similarity	NPC474164
0.6867	Remote Similarity	NPC260474
0.6867	Remote Similarity	NPC188292
0.6867	Remote Similarity	NPC310992
0.6854	Remote Similarity	NPC477371
0.6848	Remote Similarity	NPC214043
0.6848	Remote Similarity	NPC82902
0.6848	Remote Similarity	NPC221758
0.6848	Remote Similarity	NPC59453
0.6848	Remote Similarity	NPC85774
0.6835	Remote Similarity	NPC127582
0.6824	Remote Similarity	NPC5701
0.6824	Remote Similarity	NPC181204
0.6824	Remote Similarity	NPC225467
0.6813	Remote Similarity	NPC260956
0.6813	Remote Similarity	NPC193347
0.6813	Remote Similarity	NPC3511
0.6813	Remote Similarity	NPC311092
0.6813	Remote Similarity	NPC472867
0.6813	Remote Similarity	NPC142253
0.679	Remote Similarity	NPC475124
0.679	Remote Similarity	NPC212210
0.679	Remote Similarity	NPC285371
0.6786	Remote Similarity	NPC256846
0.6778	Remote Similarity	NPC472478
0.6778	Remote Similarity	NPC250632
0.6774	Remote Similarity	NPC29447
0.6774	Remote Similarity	NPC471224
0.6774	Remote Similarity	NPC469948
0.6774	Remote Similarity	NPC474218
0.6774	Remote Similarity	NPC470223
0.6762	Remote Similarity	NPC24596
0.6739	Remote Similarity	NPC83569
0.6739	Remote Similarity	NPC41539
0.6739	Remote Similarity	NPC69279
0.6729	Remote Similarity	NPC79238
0.6709	Remote Similarity	NPC276764
0.6709	Remote Similarity	NPC472304
0.6705	Remote Similarity	NPC469796
0.6705	Remote Similarity	NPC474463
0.6705	Remote Similarity	NPC469793
0.6703	Remote Similarity	NPC477372
0.6702	Remote Similarity	NPC470050
0.6702	Remote Similarity	NPC474732
0.6702	Remote Similarity	NPC470051
0.6702	Remote Similarity	NPC31564
0.6702	Remote Similarity	NPC145879
0.6702	Remote Similarity	NPC51014
0.6702	Remote Similarity	NPC474778
0.6702	Remote Similarity	NPC469994
0.6702	Remote Similarity	NPC474733
0.6667	Remote Similarity	NPC473246
0.6667	Remote Similarity	NPC237712
0.6667	Remote Similarity	NPC87141
0.6667	Remote Similarity	NPC16287
0.6667	Remote Similarity	NPC124358
0.6667	Remote Similarity	NPC87552
0.6667	Remote Similarity	NPC135005
0.6667	Remote Similarity	NPC144258
0.6667	Remote Similarity	NPC181743
0.6667	Remote Similarity	NPC178025
0.6667	Remote Similarity	NPC472306
0.6667	Remote Similarity	NPC159497
0.6636	Remote Similarity	NPC472313
0.6635	Remote Similarity	NPC475239
0.6632	Remote Similarity	NPC475740
0.6632	Remote Similarity	NPC90652
0.6632	Remote Similarity	NPC317590
0.6632	Remote Similarity	NPC58063
0.6632	Remote Similarity	NPC93778
0.6632	Remote Similarity	NPC136948
0.6632	Remote Similarity	NPC96496

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 NPC21667 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	95
0.1-0.2	872
0.2-0.3	4351
0.3-0.4	2858
0.4-0.5	669
0.5-0.6	211
0.6-0.7	84
0.7-0.8	10
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
0.775	Intermediate Similarity	NPD4747	Approved
0.7722	Intermediate Similarity	NPD3621	Clinical (unspecified phase)
0.7625	Intermediate Similarity	NPD4137	Phase 3
0.7531	Intermediate Similarity	NPD4691	Approved
0.75	Intermediate Similarity	NPD3527	Clinical (unspecified phase)
0.747	Intermediate Similarity	NPD5733	Approved
0.7447	Intermediate Similarity	NPD5769	Clinical (unspecified phase)
0.7262	Intermediate Similarity	NPD4058	Approved
0.7262	Intermediate Similarity	NPD4687	Approved
0.7229	Intermediate Similarity	NPD5276	Approved
0.6848	Remote Similarity	NPD4786	Approved
0.6813	Remote Similarity	NPD4223	Phase 3
0.6813	Remote Similarity	NPD4221	Approved
0.6774	Remote Similarity	NPD5329	Approved
0.6703	Remote Similarity	NPD8028	Phase 2
0.6702	Remote Similarity	NPD6098	Approved
0.6667	Remote Similarity	NPD4197	Approved
0.663	Remote Similarity	NPD3667	Approved
0.6562	Remote Similarity	NPD6672	Approved
0.6562	Remote Similarity	NPD5737	Approved
0.6556	Remote Similarity	NPD4777	Suspended
0.6556	Remote Similarity	NPD4776	Phase 2
0.6526	Remote Similarity	NPD4693	Phase 3
0.6526	Remote Similarity	NPD7521	Approved
0.6526	Remote Similarity	NPD5330	Approved
0.6526	Remote Similarity	NPD4689	Approved
0.6526	Remote Similarity	NPD7146	Approved
0.6526	Remote Similarity	NPD7334	Approved
0.6526	Remote Similarity	NPD6684	Approved
0.6526	Remote Similarity	NPD4138	Approved
0.6526	Remote Similarity	NPD4688	Approved
0.6526	Remote Similarity	NPD6409	Approved
0.6526	Remote Similarity	NPD4690	Approved
0.6526	Remote Similarity	NPD5205	Approved
0.6512	Remote Similarity	NPD6939	Phase 2
0.6512	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.6495	Remote Similarity	NPD5328	Approved
0.6495	Remote Similarity	NPD6673	Approved
0.6495	Remote Similarity	NPD6080	Approved
0.6495	Remote Similarity	NPD6904	Approved
0.6489	Remote Similarity	NPD3133	Approved
0.6489	Remote Similarity	NPD3666	Approved
0.6489	Remote Similarity	NPD3668	Phase 3
0.6489	Remote Similarity	NPD3665	Phase 1
0.6429	Remote Similarity	NPD4096	Approved
0.6392	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.6392	Remote Similarity	NPD6903	Approved
0.6392	Remote Similarity	NPD5208	Approved
0.6374	Remote Similarity	NPD3617	Approved
0.6364	Remote Similarity	NPD6079	Approved
0.6354	Remote Similarity	NPD5690	Phase 2
0.6354	Remote Similarity	NPD3618	Phase 1
0.6354	Remote Similarity	NPD4694	Approved
0.6354	Remote Similarity	NPD5280	Approved
0.6327	Remote Similarity	NPD4753	Phase 2
0.6304	Remote Similarity	NPD7155	Clinical (unspecified phase)
0.63	Remote Similarity	NPD6399	Phase 3
0.6275	Remote Similarity	NPD5349	Clinical (unspecified phase)
0.625	Remote Similarity	NPD4243	Approved
0.625	Remote Similarity	NPD5365	Phase 2
0.62	Remote Similarity	NPD5693	Phase 1
0.62	Remote Similarity	NPD6050	Approved
0.6186	Remote Similarity	NPD5279	Phase 3
0.6186	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.6176	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6173	Remote Similarity	NPD287	Approved
0.617	Remote Similarity	NPD4139	Approved
0.617	Remote Similarity	NPD857	Phase 3
0.617	Remote Similarity	NPD4692	Approved
0.6139	Remote Similarity	NPD4202	Approved
0.6129	Remote Similarity	NPD4195	Approved
0.6111	Remote Similarity	NPD4785	Approved
0.6111	Remote Similarity	NPD7333	Discontinued
0.6111	Remote Similarity	NPD4784	Approved
0.61	Remote Similarity	NPD5207	Approved
0.61	Remote Similarity	NPD5692	Phase 3
0.6095	Remote Similarity	NPD6404	Discontinued
0.6078	Remote Similarity	NPD6001	Approved
0.6064	Remote Similarity	NPD4695	Discontinued
0.6058	Remote Similarity	NPD6083	Phase 2
0.6058	Remote Similarity	NPD6084	Phase 2
0.6044	Remote Similarity	NPD6942	Approved
0.6044	Remote Similarity	NPD7339	Approved
0.6042	Remote Similarity	NPD4788	Approved
0.604	Remote Similarity	NPD5284	Approved
0.604	Remote Similarity	NPD5694	Approved
0.604	Remote Similarity	NPD5281	Approved
0.602	Remote Similarity	NPD4519	Discontinued
0.602	Remote Similarity	NPD4623	Approved
0.6019	Remote Similarity	NPD7812	Clinical (unspecified phase)
0.6019	Remote Similarity	NPD4629	Approved
0.6019	Remote Similarity	NPD5210	Approved
0.5962	Remote Similarity	NPD5221	Approved
0.5962	Remote Similarity	NPD5222	Approved
0.5962	Remote Similarity	NPD5220	Clinical (unspecified phase)
0.5962	Remote Similarity	NPD4697	Phase 3
0.5922	Remote Similarity	NPD5771	Approved
0.5905	Remote Similarity	NPD4755	Approved
0.5905	Remote Similarity	NPD5173	Approved
0.587	Remote Similarity	NPD5275	Approved
0.587	Remote Similarity	NPD4190	Phase 3
0.5865	Remote Similarity	NPD5695	Phase 3
0.5849	Remote Similarity	NPD5696	Approved
0.5825	Remote Similarity	NPD5133	Approved
0.581	Remote Similarity	NPD7614	Phase 1
0.581	Remote Similarity	NPD7732	Phase 3
0.58	Remote Similarity	NPD3573	Approved
0.5794	Remote Similarity	NPD4700	Approved
0.5794	Remote Similarity	NPD5286	Approved
0.5794	Remote Similarity	NPD4696	Approved
0.5794	Remote Similarity	NPD5285	Approved
0.578	Remote Similarity	NPD6052	Approved
0.5772	Remote Similarity	NPD6330	Clinical (unspecified phase)
0.5769	Remote Similarity	NPD5707	Approved
0.5758	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.5755	Remote Similarity	NPD4657	Approved
0.5755	Remote Similarity	NPD4655	Approved
0.5743	Remote Similarity	NPD4518	Approved
0.5743	Remote Similarity	NPD4722	Approved
0.5743	Remote Similarity	NPD4723	Approved
0.5741	Remote Similarity	NPD5223	Approved
0.5728	Remote Similarity	NPD7515	Phase 2
0.5714	Remote Similarity	NPD7148	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD7147	Phase 3
0.5714	Remote Similarity	NPD5654	Approved
0.5688	Remote Similarity	NPD6024	Approved
0.5688	Remote Similarity	NPD5211	Phase 2
0.5688	Remote Similarity	NPD5226	Approved
0.5688	Remote Similarity	NPD6027	Approved
0.5688	Remote Similarity	NPD4633	Approved
0.5688	Remote Similarity	NPD5225	Approved
0.5688	Remote Similarity	NPD5224	Approved
0.5688	Remote Similarity	NPD5091	Approved
0.5686	Remote Similarity	NPD7285	Clinical (unspecified phase)
0.5684	Remote Similarity	NPD1402	Approved
0.568	Remote Similarity	NPD6914	Discontinued
0.5676	Remote Similarity	NPD7128	Approved
0.5676	Remote Similarity	NPD6402	Approved
0.5676	Remote Similarity	NPD6675	Approved
0.5676	Remote Similarity	NPD5739	Approved
0.5667	Remote Similarity	NPD6923	Approved
0.5667	Remote Similarity	NPD6922	Approved
0.5667	Remote Similarity	NPD6909	Approved
0.5667	Remote Similarity	NPD6908	Approved
0.5652	Remote Similarity	NPD7336	Phase 2
0.5652	Remote Similarity	NPD7335	Phase 2
0.5652	Remote Similarity	NPD7337	Clinical (unspecified phase)
0.5638	Remote Similarity	NPD3701	Clinical (unspecified phase)
0.5636	Remote Similarity	NPD4754	Approved
0.5636	Remote Similarity	NPD5175	Approved
0.5636	Remote Similarity	NPD5174	Approved
0.5631	Remote Similarity	NPD6934	Discontinued
0.5625	Remote Similarity	NPD6614	Approved
0.5619	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5619	Remote Similarity	NPD7748	Approved
0.5619	Remote Similarity	NPD7900	Approved
0.5607	Remote Similarity	NPD5959	Approved
0.5604	Remote Similarity	NPD7144	Approved
0.5604	Remote Similarity	NPD7143	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